Tetrahydro-imidazo quinoline compositions as cbp/p300 inhibitors

ABSTRACT

The present disclosure is directed to inhibitors of the CBP/p300 family of bromodomains. The compounds can be useful in the treatment of disease or disorders associated with the inhibition of the CBP/p300 family of bromodomains. For instance, the disclosure is concerned with compounds and compositions for inhibition of the CBP/p300 family of bromodomains, methods of treating, preventing, or ameliorating diseases or disorders associated with the inhibition of CBP/p300 family of bromodomains, and methods of synthesis of these compounds.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/647,478, filed Mar. 13, 2020, which is a National Stage applicationof International Application No. PCT/US2018/051235, filed Sep. 14, 2018,which claims the benefit of priority of U.S. Provisional Application No.62/559,436, filed Sep. 15, 2017 and U.S. Provisional Application No.62/692,593, filed Jun. 29, 2018, all of which are incorporated herein byreference in their entireties.

FIELD OF DISCLOSURE

The present disclosure is directed to inhibitors of the CBP/p300 familyof bromodomains useful in the treatment of disease or disordersassociated with the inhibition of the CBP/p300 family of bromodomains.Specifically, the disclosure is concerned with compounds andcompositions for inhibition of the CBP/p300 family of bromodomains,methods of treating, preventing, or ameliorating diseases or disordersassociated with the inhibition of CBP/p300 family of bromodomains, andmethods of synthesis of these compounds.

BACKGROUND OF DISCLOSURE

p300 (also known as EP300 and KAT3B) is a large protein with multipledomains that bind to diverse proteins including many DNA-bindingtranscription factors. The cyclic AMP-responsive element-binding protein(CREB) binding protein (CBP, also known as KAT3A) is a cellular paralogof p300. p300 and CBP share extensive sequence identity and functionalsimilarity. As such, they are often referred to as CBP/p300 in thescientific literature. CBP/p300 are lysine acetyltransferases thatcatalyze the attachment of an acetyl group to a lysine side chain ofhistones and other protein substrates. As large proteins, CBP/p300 wereproposed to activate transcription in part by bridging DNA-bindingtranscription factors to RNA polymerase machinery or by helping assemblethe transcriptional pre-initiation complex (PIC). Importantly,CBP/p300-catalyzed acetylation of histones and other proteins is pivotalto gene activation. Heightened p300 expression and activities have beenobserved in advanced human cancers such as prostate and liver (cancerand appear to be associated with poor prognosis of these cancer types.Compared to normal tissue counterparts, the expression levels of p300are higher in human primary breast cancer specimens and in mouse mammarycarcinomas induced by polyomavirus middle-T oncogene.

SUMMARY OF DISCLOSURE

Novel compounds useful for inhibiting CBP, including CBP InhibitorCompounds and Selective CBP Inhibitor Compounds, are disclosed herein. Afirst aspect of the present disclosure relates to compounds of Formula(I):

or a pharmaceutically acceptable salt, enantiomer, hydrate, solvate,isomer, or tautomer thereof,

wherein:

R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, —OR⁵, —N(R⁵)₂, or—NHR⁵;

R² is —H, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, or aryl, wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R⁶;

R³ is —H, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl,heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R⁷;

R⁴ and R^(4′) are each independently —H, halogen, —OH, —CN, or —NH₂;

each R⁵ is independently —C₁-C₆alkyl, —C₃-C₈cycloalkyl, heterocyclyl,aryl, or heteroaryl;

R⁶ and R⁷ are each independently, at each occurrence, —C₁-C₆alkyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, heteroaryl, —OH, halogen, oxo, —CN,—SR⁸, —OR⁸, —(CH₂)_(n)—OR⁸, —NHR⁸, —NR⁸R⁹, —S(O)₂NR⁸R⁹, —S(O)₂R^(8′),—C(O)R^(8′), —C(O)OR⁸, —C(O)NR⁸R⁹, —NR⁸C(O)R^(9′), —NR⁸S(O)₂R^(9′),—S(O)R^(8′), —S(O)NR⁸R⁹, or —NR'S(O)R^(9′), wherein each alkyl,cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R¹⁰;

wherein any two R⁶ or any two R⁷, when on non-adjacent atoms, cancombine to form a bridging cycloalkyl or heterocyclyl;

wherein any two R⁶ or any two R⁷, when on adjacent atoms, can combine toform a cycloalkyl, heterocyclyl, aryl or heteroaryl;

R⁸ and R⁹ are each independently, at each occurrence, —H, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl isoptionally substituted with one or more R¹⁰ or R¹¹; or

R⁸ and R⁹ may combine with the atom to which they are both attached toform a —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰ or R¹¹;

R^(8′) and R^(9′) are each independently, at each occurrence,—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl,alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, orheteroaryl is optionally substituted with one or more R¹⁰ or R¹¹; or

R⁸ and R^(9′) may combine with the atom to which they are both attachedto form a —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰ or R¹¹; R¹⁰ and R¹¹ are eachindependently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—OC₃-C₆cycloalkyl, -Oaryl, -Oheteroaryl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl,—C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂,—C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl),—S(O)N(C₁-C₆alkyl)₂, or —N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more —R¹²;

wherein any two R¹⁰ or any two R¹¹, when on non-adjacent atoms, cancombine to form a bridging cycloalkyl or heterocyclyl;

wherein any two R¹⁰ or any two R¹¹, when on adjacent atoms, can combineto form a cycloalkyl, heterocyclyl, aryl or heteroaryl;

R¹² is independently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl),—S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl); and n is an integer from 1 to 4.

Another aspect of the present disclosure relates to a pharmaceuticalcomposition comprising a compound of Formula (I), or a pharmaceuticallyacceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomerthereof and a pharmaceutically acceptable carrier. The pharmaceuticallyacceptable carrier can further include an excipient, diluent, orsurfactant. The pharmaceutical composition can be effective for treatinga disease or disorder associated with CBP/p300 modulation in a subjectin need thereof. The pharmaceutical compositions can comprise thecompounds of the present disclosure for use in treating diseasesdescribed herein. The compositions can contain at least one compound ofthe disclosure and a pharmaceutically acceptable carrier.

In another aspect, the present disclosure relates to a method ofmodulating one or more of CBP/p300-family bromodomains. The method cancomprise administering to a patient in need thereof a therapeuticallyeffective amount of a compound of Formula (I), or a pharmaceuticallyacceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomerthereof. Another aspect of the present disclosure relates to a method ofinhibiting one or more of CBP/p300-family bromodomains. The method cancomprise administering to a patient in need thereof a therapeuticallyeffective amount of a compound of Formula (I), or a pharmaceuticallyacceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomerthereof. In another aspect, the present disclosure relates to a methodof inhibiting one or more of CBP/p300-family bromodomains. The methodcan comprise administering to a patient in need thereof atherapeutically effective amount of a pharmaceutical compositiondescribed herein.

Another aspect of the present disclosure relates to a method oftreating, preventing, inhibiting, or eliminating a disease or conditionin a patient associated with the inhibition of one or more ofCBP/p300-family bromodomains. The method can comprise administering to apatient in need thereof a therapeutically effective amount of a compounddisclosed herein, such as a compound of Formula (I), or apharmaceutically acceptable salt, hydrate, solvate, prodrug,stereoisomer, or tautomer thereof, wherein said disease or condition isselected from the group consisting of cancer

The present disclosure further provides compounds and compositions withan improved efficacy and safety profile relative to known CBP/p300domain inhibitors. The present disclosure also provides agents withnovel mechanisms of action toward CBP/p300 proteins in the treatment ofvarious types of diseases including cancers. The present disclosure canprovide the medical community with a novel pharmacological strategy forthe treatment of diseases and disorders associated with inhibition ofCBP/p300 proteins, including the inhibition of CBP in the HTRFbiochemical assay of Example 963 disclosed herein, with an IC₅₀ value of0.001-1 micromolar.

DETAILED DESCRIPTION OF THE DISCLOSURE

The present disclosure relates to compounds and compositions that arecapable of modulating the activity of the CBP/p300 family bromodomains.The disclosure features methods of treating, preventing or amelioratinga disease or disorder in which CBP/p300 bromodomains play a role byadministering to a patient in need thereof a therapeutically effectiveamount of a compound of Formula (I), or a pharmaceutically acceptablesalt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. Themethods of the present disclosure can be used in the treatment of avariety of CBP/p300 bromodomain dependent diseases and disorders byinhibiting the activity of a CBP/p300 bromodomains. Inhibition ofCBP/p300 bromodomains provides a novel approach to the treatment,prevention, or amelioration of diseases including, but not limited to,cancer, inflammatory diseases, diabetes and obesity, and to develop malecontraceptives.

The details of the disclosure are set forth in the accompanyingdescription below. Although methods and materials similar or equivalentto those described herein can be used in the practice or testing of thepresent disclosure, illustrative methods and materials are nowdescribed. Other features, objects, and advantages of the disclosurewill be apparent from the description and from the claims. In thespecification and the appended claims, the singular forms also includethe plural unless the context clearly dictates otherwise. Unless definedotherwise, all technical and scientific terms used herein have the samemeaning as commonly understood by one of ordinary skill in the art towhich this disclosure belongs. All patents and publications cited inthis specification are incorporated herein by reference in theirentireties.

Definitions

Unless otherwise indicated, “CBP Inhibitor Compound” as used hereinrefers to a compound having one or more of the following characteristicswhen tested according to the HTRF biochemical Assay Protocol of Example963 below: (1) a CBP IC₅₀ value of less than 1 μM; and (2) a CBP IC₅₀value of between 0.001 and 1 μM.

Unless otherwise indicated, a “Selective CBP Inhibitor Compound” as usedherein refers to a CBP Inhibitor having a BRD4 IC₅₀ value greater thanthat of its CBP IC₅₀ value, preferably wherein its BRD4 IC₅₀ valuegreater than 1 μM (e.g., 1 micromolar to 10 micomolar, or greater),wherein the IC₅₀ values are as determined in the procedures set forth inExample 963.

The articles “a” and “an” are used in this disclosure to refer to one ormore than one (i.e., to at least one) of the grammatical object of thearticle. By way of example, “an element” means one element or more thanone element.

The term “and/or” is used in this disclosure to mean either “and” or“or” unless indicated otherwise.

The term “optionally substituted” is understood to mean that a givenchemical moiety (e.g. an alkyl group) can (but is not required to) bebonded other substituents (e.g. heteroatoms). For instance, an alkylgroup that is optionally substituted can be a fully saturated alkylchain (i.e. a pure hydrocarbon). Alternatively, the same optionallysubstituted alkyl group can have substituents different from hydrogen.For instance, it can, at any point along the chain be bonded to ahalogen atom, a hydroxyl group, or any other substituent describedherein. Thus the term “optionally substituted” means that a givenchemical moiety has the potential to contain other functional groups,but does not necessarily have any further functional groups.

The term “aryl” refers to cyclic, aromatic hydrocarbon groups that have1 to 2 aromatic rings, including monocyclic or bicyclic groups. In someembodiments, aryl groups have a total of 5 to 14 ring members, whereinat least one ring in the system is aromatic and wherein each ring in thesystem contains three to seven ring members. Where containing twoaromatic rings (bicyclic, etc.), the aromatic rings of the aryl groupmay be joined at a single point (e.g., biphenyl), or fused (e.g.,naphthyl). The aryl group may be optionally substituted by one or moresubstituents, e.g., 1 to 5 substituents, at any point of attachment.Exemplary substituents include, but are not limited to, —H, -halogen,—O—C₁-C₆alkyl, —C₁-C₆alkyl, —OC₂-C₆alkenyl, —OC₂-C₆alkynyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —OH, —OP(O)(OH)₂, —OC(O)C₁-C₆alkyl,—C(O)C₁-C₆alkyl, —OC(O)OC₁-C₆alkyl, —NH₂, —NH(C₁-C₆alkyl),—N(C₁-C₆alkyl)₂, —S(O)₂—C₁-C₆alkyl, —S(O)NHC₁-C₆alkyl, and—S(O)N(C₁-C₆alkyl)₂. The substituents can themselves be optionallysubstituted. Furthermore when containing two fused rings the aryl groupsherein defined may have an unsaturated or partially saturated ring fusedwith a fully saturated ring. Exemplary ring systems of these aryl groupsinclude indanyl, indenyl, tetrahydronaphthalenyl, andtetrahydrobenzoannulenyl.

Unless otherwise specifically defined, “heteroaryl” means a monovalentmonocyclic aromatic radical or a polycyclic aromatic radical of 5 to 24ring atoms, containing one or more ring heteroatoms selected from N, S,P, and O, the remaining ring atoms being C. Heteroaryl as herein definedalso means a bicyclic heteroaromatic group wherein the heteroatom isselected from N, S, P, and O. The aromatic radical is optionallysubstituted independently with one or more substituents describedherein. Examples include, but are not limited to, furyl, thienyl,pyrrolyl, pyridyl, pyrazolyl, pyrimidinyl, imidazolyl, isoxazolyl,oxazolyl, oxadiazolyl, pyrazinyl, indolyl, thiophen-2-yl, quinolyl,benzopyranyl, isothiazolyl, thiazolyl, thiadiazole, indazole,benzimidazolyl, thieno[3,2-b]thiophene, triazolyl, triazinyl,imidazo[1,2-b]pyrazolyl, furo[2,3-c]pyridinyl, imidazo[1,2-a]pyridinyl,indazolyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-c]pyridinyl,pyrazolo[3,4-c]pyridinyl, thieno[3,2-c]pyridinyl,thieno[2,3-c]pyridinyl, thieno[2,3-b]pyridinyl, benzothiazolyl, indolyl,indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuranyl,benzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl,dihydrobenzothiazine, dihydrobenzoxanyl, quinolinyl, isoquinolinyl,1,6-naphthyridinyl, benzo[de]isoquinolinyl,pyrido[4,3-b][1,6]naphthyridinyl, thieno[2,3-b]pyrazinyl, quinazolinyl,tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, isoindolyl,pyrrolo[2,3-b]pyridinyl, pyrrolo[3,4-b]pyridinyl,pyrrolo[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl,pyrrolo[1,2-a]pyrimidinyl, tetrahydro pyrrolo[1,2-a]pyrimidinyl,3,4-dihydro-2H-1λ²-pyrrolo[2,1-b]pyrimidine, dibenzo[b,d]thiophene,pyridin-2-one, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl,1H-pyrido[3,4-b][1,4]thiazinyl, benzooxazolyl, benzoisoxazolyl,furo[2,3-b]pyridinyl, benzothiophenyl, 1,5-naphthyridinyl,furo[3,2-b]pyridine, [1,2,4]triazolo[1,5-a]pyridinyl, benzo[1,2,3]triazolyl, imidazo[1,2-a]pyrimidinyl,[1,2,4]triazolo[4,3-b]pyridazinyl, benzo[c][1,2,5]thiadiazolyl,benzo[c][1,2,5]oxadiazole, 1,3-dihydro-2H-benzo[d]imidazol-2-one,3,4-dihydro-2H-pyrazolo [1,5-b][1,2]oxazinyl,4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl, thiazolo[5,4-d]thiazolyl,imidazo[2,1-b][1,3,4]thiadiazolyl, thieno[2,3-b]pyrrolyl, 3H-indolyl,and derivatives thereof.

Furthermore when containing two fused rings the heteroaryl groups hereindefined may have an unsaturated or partially saturated ring fused with afully saturated ring. Exemplary ring systems of these heteroaryl groupsinclude indolinyl, indolinonyl, dihydrobenzothiophenyl,dihydrobenzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl,dihydrobenzothiazine, 3,4-dihydro-1H-isoquinolinyl,2,3-dihydrobenzofuran, indolinyl, indolyl, and dihydrobenzoxanyl. Insome embodiments, “heteroaryl” refers to groups having 5 to 10 ringatoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14π electronsshared in a cyclic array; and/or having, in addition to carbon atoms,from one to five heteroatoms wherein the term “heteroatom” refers tonitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogenor sulfur, and any quaternized form of a basic nitrogen.

“Alkyl” refers to a straight or branched chain saturated hydrocarboncontaining 1-12 carbon atoms. C₁-C₆alkyl groups contain 1 to 6 carbonatoms. Examples of a C₁-C₆alkyl group include, but are not limited to,methyl, ethyl, propyl, butyl, pentyl, isopropyl, isobutyl, sec-butyl andtert-butyl, isopentyl and neopentyl.

“Alkenyl” refers to a straight or branched chain unsaturated hydrocarboncontaining 2-12 carbon atoms. The “alkenyl” group contains at least onedouble bond in the chain. The double bond of an alkenyl group can beunconjugated or conjugated to another unsaturated group.

Examples of alkenyl groups include ethenyl, propenyl, n-butenyl,iso-butenyl, pentenyl, or hexenyl. An alkenyl group can be unsubstitutedor substituted. Alkenyl, as herein defined, may be straight or branched.

“Alkynyl” refers to a straight or branched chain unsaturated hydrocarboncontaining 2-12 carbon atoms. The “alkynyl” group contains at least onetriple bond in the chain. Examples of alkenyl groups include ethynyl,propanyl, n-butynyl, iso-butynyl, pentynyl, or hexynyl. An alkynyl groupcan be unsubstituted or substituted.

The term “cycloalkyl” means monocyclic or polycyclic saturated carbonrings containing 3-18 carbon atoms. Examples of cycloalkyl groupsinclude, without limitations, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptanyl, cyclooctanyl, norboranyl, norborenyl,bicyclo[2.2.2]octanyl, or bicyclo[2.2.2]octenyl. A C₃-C₈ cycloalkyl is acycloalkyl group containing between 3 and 8 carbon atoms. A cycloalkylgroup can be fused (e.g., decalin) or bridged (e.g., norbornane).

The term “cycloalkenyl” means monocyclic, non-aromatic unsaturatedcarbon rings containing 4-18 carbon atoms. Examples of cycloalkenylgroups include, without limitation, cyclopentenyl, cyclohexenyl,cycloheptenyl, cyclooctenyl, and norborenyl. A C₄-C₈ cycloalkenyl is acycloalkenyl group containing between 4 and 8 carbon atoms.

The terms “heterocyclyl” or “heterocycloalkyl” or “heterocycle” refer tomonocyclic or polycyclic 3 to 24-membered rings containing carbon andheteroatoms taken from oxygen, phosphorous, nitrogen, or sulfur andwherein there is not delocalized π electrons (aromaticity) shared amongthe ring carbon or heteroatoms. In some embodiments, “heterocyclyl”refers to a stable 5- to 7-membered monocyclic or 7-10-membered bicyclicheterocyclic moiety that is either saturated or partially unsaturated,and having, in addition to carbon atoms, one or more, preferably one tofour, heteroatoms selected from N, S, P, or O. Heterocyclyl rings can befully saturated or partially unsaturated. Heterocyclyl rings include,but are not limited to, oxetanyl, azetadinyl, tetrahydrofuranyl,pyrrolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl,pyranyl, thiopyranyl, tetrahydropyranyl, dioxalinyl, piperidinyl,morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinylS-dioxide, piperazinyl, azepinyl, oxepinyl, diazepinyl, tropanyl,pyridonyl, and homotropanyl. A heteroycyclyl or heterocycloalkyl ringcan also be fused or bridged, e.g., can be a bicyclic ring.

As used herein, the term “partially unsaturated” refers to a ring moietythat includes at least one double or triple bond. The term “partiallyunsaturated” is intended to encompass rings having multiple sites ofunsaturation, but is not intended to include aryl or heteroarylmoieties, as herein defined.

The term “spirocycle” is understood as a bicyclic ring system with bothrings connected through a single atom. A spirocycle can be fullysaturated or can be partially unsaturated.

The term “spirocycloalkyl” is understood to mean a fully carbogenicbicyclic ring systems with both rings connected through a single atom.The ring can be different in size and nature, or identical in size andnature. Examples include spiropentane, spriohexane, spiroheptane,spirooctane, spirononane, or spirodecane. One or both of the rings in aspirocycloalkyl can be fused to another ring carbocyclic, heterocyclic,aromatic, or heteroaromatic ring. A (C₅-C₁₂) spirocycloalkyl is aspirocycle containing between 5 and 12 carbon atoms.

The term “spiroheterocycloalkyl” or “spiroheterocyclyl” is understood tomean a spirocycle as defined above wherein at least one of the rings isa heterocycle (e.g., at least one of the rings is furanyl, morpholinyl,or piperadinyl). Spiroheterocycloalkyl groups can be for instance,without limitation, azapiroheptanes; azaspirooctanes; azaspirononanes;azaspirodecanes; oxaspiroheptanes; oxaspirooctanes; octaspirononanes; oroxaspirodecanes.

As used herein, the term “halo” or “halogen” means a fluoro, chloro,bromo, or iodo group.

The term “carbonyl” refers to a functional group composing a carbon atomdouble-bonded to an oxygen atom. It can be abbreviated herein as C(O),or as C═O.

The term “oxo” refers to an oxygen atom that is double-bonded to anotheratom. An “oxo” group can be connected to a carbon atom (e.g., to form acarbonyl, as defined above) or can be connected to a heteroatom such assulfur (e.g., to form a sulfoxide or a sulfone) or phosphorous (e.g., toform a phosphorous ylide).

The disclosure also includes pharmaceutical compositions comprising aneffective amount of a disclosed compound and a pharmaceuticallyacceptable carrier. Representative “pharmaceutically acceptable salts”include, e.g., water-soluble and water-insoluble salts, such as theacetate, amsonate (4,4-diaminostilbene-2,2-disulfonate),benzenesulfonate, benzonate, bicarbonate, bisulfate, bitartrate, borate,bromide, butyrate, calcium, calcium edetate, camsylate, carbonate,chloride, citrate, clavulariate, dihydrochloride, edetate, edisylate,estolate, esylate, fiunarate, gluceptate, gluconate, glutamate,glycollylarsanilate, hexafluorophosphate, hexylresorcinate, hydrabamine,hydrobromide, hydrochloride, hydroxynaphthoate, iodide, sethionate,lactate, lactobionate, laurate, magnesium, malate, maleate, mandelate,mesylate, methylbromide, methylnitrate, methylsulfate, mucate,napsylate, nitrate, N-methylglucamine ammonium salt,3-hydroxy-2-naphthoate, oleate, oxalate, palmitate, pamoate(1,1-methene-bis-2-hydroxy-3-naphthoate, einbonate), pantothenate,phosphate/diphosphate, picrate, polygalacturonate, propionate,p-toluenesulfonate, salicylate, stearate, subacetate, succinate,sulfate, sulfosalicylate, suramate, tannate, tartrate, teoclate,tosylate, triethiodide, and valerate salts.

The term “tautomers” refers to a set of compounds that have the samenumber and type of atoms, but differ in bond connectivity and are inequilibrium with one another. A “tautomer” is a single member of thisset of compounds. Typically a single tautomer is drawn but it isunderstood that this single structure is meant to represent all possibletautomers that might exist. Examples include enol-ketone tautomerism.When a ketone is drawn it is understood that both the enol and ketoneforms are part of the disclosure.

The term “prodrug,” as used in this disclosure, means a compound whichis convertible in vivo by metabolic means (e.g., by hydrolysis) to adisclosed compound. Furthermore, as used herein a prodrug is a drugwhich is inactive in the body, but is transformed in the body typicallyeither during absorption or after absorption from the gastrointestinaltract into the active compound. The conversion of the prodrug into theactive compound in the body may be done chemically or biologically(i.e., using an enzyme).

The term “solvate” refers to a complex of variable stoichiometry formedby a solute and solvent. Such solvents for the purpose of the disclosuremay not interfere with the biological activity of the solute. Examplesof suitable solvents include, but are not limited to, water, MeOH, EtOH,and AcOH. Solvates wherein water is the solvent molecule are typicallyreferred to as hydrates. Hydrates include compositions containingstoichiometric amounts of water, as well as compositions containingvariable amounts of water.

The term “isomer” refers to compounds that have the same composition andmolecular weight but differ in physical and/or chemical properties. Thestructural difference may be in constitution (geometric isomers) or inthe ability to rotate the plane of polarized light (stereoisomers). Withregard to stereoisomers, the compounds of Formula (I) may have one ormore asymmetric carbon atom and may occur as racemates, racemic mixturesand as individual enantiomers or diastereomers.

The term “stereoisomers” refers to the set of compounds which have thesame number and type of atoms and share the same bond connectivitybetween those atoms, but differ in three dimensional structure. The term“stereoisomer” refers to any member of this set of compounds. Forinstance, a stereoisomer may be an enantiomer or a diastereomer.

The term “enantiomers” refers to a pair of stereoisomers which arenon-superimposable mirror images of one another. The term “enantiomer”refers to a single member of this pair of stereoisomers. The term“racemic” refers to a 1:1 mixture of a pair of enantiomers.

The term “diastereomers” refers to the set of stereoisomers which cannotbe made superimposable by rotation around single bonds. Diastereomerismoccurs when two or more stereoisomers of a compound have differentconfigurations at one or more (but not all) of the equivalent (related)stereocenters and are not mirror images of each other. Compoundscontaining multiple stereogenic centers with different relativeconfigurations are considered to be diastereomers. The term“diastereomer” refers to any member of this set of compounds. In someexamples presented, the synthetic route may produce a singlediastereomer or a mixture of diastereomers. In some cases thesediastereomers were separated and in other cases a wavy bond is used toindicate the structural element where configuration is variable.

An “effective amount” when used in connection with a compound is anamount effective for treating or preventing a disease in a subject asdescribed herein.

The term “carrier”, as used in this disclosure, encompasses carriers,excipients, and diluents and means a material, composition or vehicle,such as a liquid or solid filler, diluent, excipient, solvent orencapsulating material, involved in carrying or transporting apharmaceutical agent from one organ, or portion of the body, to anotherorgan, or portion of the body of a subject.

The term “treating” with regard to a subject, refers to improving atleast one symptom of the subject's disorder. Treating includes curing,improving, or at least partially ameliorating the disorder.

The term “disorder” is used in this disclosure to mean, and is usedinterchangeably with, the terms disease, condition, or illness, unlessotherwise indicated.

The term “administer”, “administering”, or “administration” as used inthis disclosure refers to either directly administering a disclosedcompound or pharmaceutically acceptable salt of the disclosed compoundor a composition to a subject, or administering a prodrug derivative oranalog of the compound or pharmaceutically acceptable salt of thecompound or composition to the subject, which can form an equivalentamount of active compound within the subject's body.

A “patient” or “subject” is a mammal, e.g., a human, mouse, rat, guineapig, dog, cat, horse, cow, pig, or non-human primate, such as a monkey,chimpanzee, baboon or rhesus.

It should be understood that all isomeric forms are included within thepresent disclosure, including mixtures thereof. If the compound containsa double bond, the substituent may be in the E or Z configuration. Ifthe compound contains a disubstituted cycloalkyl, the cycloalkylsubstituent may have a cis- or trans configuration. All tautomeric formsare also intended to be included.

Compounds of Formula (I), and salts, solvates, esters and prodrugsthereof, may exist in their tautomeric form (for example, as an amide orimino ether). All such tautomeric forms are contemplated herein as partof the present disclosure.

The compounds of Formula (I), may contain asymmetric or chiral centers,and, therefore, exist in different stereoisomeric forms. It is intendedthat all stereoisomeric forms of the compounds of Formula (I) as well asmixtures thereof, including racemic mixtures, form part of the presentdisclosure. In addition, the present disclosure embraces all geometricand positional isomers. For example, if a compound of Formula (I),incorporates a double bond or a fused ring, both the cis- andtrans-forms, as well as mixtures, are embraced within the scope of thedisclosure. Each compound herein disclosed includes all the enantiomersthat conform to the general structure of the compound. The compounds maybe in a racemic or enantiomerically pure form, or any other form interms of stereochemistry. The assay results may reflect the datacollected for the racemic form, the enantiomerically pure form, or anyother form in terms of stereochemistry.

Diastereomeric mixtures can be separated into their individualdiastereomers on the basis of their physical chemical differences bymethods well known to those skilled in the art, such as, for example, bychromatography and/or fractional crystallization. Enantiomers can beseparated by converting the enantiomeric mixture into a diastereomericmixture by reaction with an appropriate optically active compound (e.g.,chiral auxiliary such as a chiral alcohol or Mosher's acid chloride),separating the diastereomers and converting (e.g., hydrolyzing) theindividual diastereomers to the corresponding pure enantiomers. Also,some of the compounds of Formula (I) may be atropisomers (e.g.,substituted biaryls) and are considered as part of this disclosure.Enantiomers can also be separated by use of a chiral HPLC column.

It is also possible that the compounds of Formula (I), may exist indifferent tautomeric forms, and all such forms are embraced within thescope of the disclosure. Also, for example, all keto-enol andimine-enamine forms of the compounds are included in the disclosure.

All stereoisomers (for example, geometric isomers, optical isomers andthe like) of the present compounds (including those of the salts,solvates, esters and prodrugs of the compounds as well as the salts,solvates and esters of the prodrugs), such as those which may exist dueto asymmetric carbons on various substituents, including enantiomericforms (which may exist even in the absence of asymmetric carbons),rotameric forms, atropisomers, and diastereomeric forms, arecontemplated within the scope of this disclosure, as are positionalisomers (such as, for example, 4-pyridyl and 3-pyridyl). (For example,if a compound of Formula (I) incorporates a double bond or a fused ring,both the cis- and trans-forms, as well as mixtures, are embraced withinthe scope of the disclosure. Also, for example, all keto-enol andimine-enamine forms of the compounds are included in the disclosure.)Individual stereoisomers of the compounds of the disclosure may, forexample, be substantially free of other isomers, or may be admixed, forexample, as racemates or with all other, or other selected,stereoisomers. The chiral centers of the present disclosure can have theS or R configuration as defined by the IUPAC 1974 Recommendations. Theuse of the terms “salt”, “solvate”, “ester,” “prodrug” and the like, isintended to equally apply to the salt, solvate, ester and prodrug ofenantiomers, stereoisomers, rotamers, tautomers, positional isomers,racemates or prodrugs of the inventive compounds.

The present disclosure also embraces isotopically-labelled compounds ofthe present disclosure which are identical to those recited herein, butfor the fact that one or more atoms are replaced by an atom having anatomic mass or mass number different from the atomic mass or mass numberusually found in nature. Examples of isotopes that can be incorporatedinto compounds of the disclosure include isotopes of hydrogen, carbon,nitrogen, oxygen, phosphorus, fluorine and chlorine, such as ²H (or D),³H, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O ³¹P, ³²P, ³⁵S, ¹⁸F, and ³⁶Cl, respectively.

Certain isotopically-labelled compounds of Formula (I) (e.g., thoselabeled with ³H and ¹⁴C) are useful in compound and/or substrate tissuedistribution assays. Tritiated (i.e., ³H) and carbon-14 (i.e., ¹⁴C)isotopes are particularly preferred for their ease of preparation anddetectability. Further, substitution with heavier isotopes such asdeuterium (i.e., ²H) may afford certain therapeutic advantages resultingfrom greater metabolic stability (e.g., increased in vivo half-life orreduced dosage requirements) and hence may be preferred in somecircumstances. Isotopically labelled compounds of Formula (I) cangenerally be prepared by following procedures analogous to thosedisclosed in the Schemes and/or in the Examples herein below, bysubstituting an appropriate isotopically labelled reagent for anon-isotopically labelled reagent.

The compounds of Formula (I) may form salts which are also within thescope of this disclosure. Reference to a compound of the Formula (I)herein is understood to include reference to salts thereof, unlessotherwise indicated.

The present disclosure relates to compounds which are modulators of oneor more bromodomains of the CBP/p300 family. In one embodiment, thecompounds of the present disclosure are inhibitors of one or morebromodomains of the CBP/p300 family.

Compounds of the Disclosure

The present disclosure relates to compounds, or pharmaceuticallyacceptable salts or isomers thereof, capable of modulating CBP/p300family bromodomains which are useful for the treatment of diseases anddisorders associated with modulation of CBP/p300 family bromodomains.The disclosure further relates to compounds, or pharmaceuticallyacceptable salts or isomers thereof, which are useful for inhibitingCBP/p300 family bromodomains.

One aspect of the present disclosure describes compounds of Formula (I):

or a pharmaceutically acceptable salt, enantiomer, hydrate, solvate,isomer, or tautomer thereof,

wherein:

R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, —OR⁵, —N(R⁵)₂, or—NHR⁵;

R² is —H, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, or aryl, wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R⁶;

R³ is —H, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl,heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R⁷;

R⁴ and R^(4′) are each independently —H, halogen, —OH, —CN, or —NH₂;

each R⁵ is independently —C₁-C₆alkyl, —C₃-C₈cycloalkyl, heterocyclyl,aryl, or heteroaryl;

R⁶ and R⁷ are each independently, at each occurrence, —C₁-C₆alkyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, heteroaryl, —OH, halogen, oxo, —CN,—SR⁸, —OR⁸, —(CH₂)_(n)—OR⁸, —NHR⁸, —NR⁸R⁹, —S(O)₂NR⁸R⁹, —S(O)₂R^(8′),—C(O)R^(8′), —C(O)OR⁸, —C(O)NR⁸R⁹, —NR⁸C(O)R^(9′), —NR'S(O)₂R^(9′),—S(O)R^(8′), —S(O)NR⁸R⁹, or —NR'S(O)R^(9′), wherein each alkyl,cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R¹⁰;

wherein any two R⁶ or any two R⁷, when on non-adjacent atoms, cancombine to form a bridging cycloalkyl or heterocyclyl;

wherein any two R⁶ or any two R⁷, when on adjacent atoms, can combine toform a cycloalkyl, heterocyclyl, aryl or heteroaryl;

R⁸ and R⁹ are each independently, at each occurrence, —H, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl isoptionally substituted with one or more R¹⁰ or R¹¹; or

R⁸ and R⁹ may combine with the atom to which they are both attached toform a —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰ or R¹¹;

R^(8′) and R^(9′) are each independently, at each occurrence,—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl,alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, orheteroaryl is optionally substituted with one or more R¹⁰ or R¹¹; or

R⁸ and R^(9′) may combine with the atom to which they are both attachedto form a —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰ or R¹¹;

R¹⁰ and R¹¹ are each independently, at each occurrence, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂,—OC₁-C₆alkyl, —OC₃-C₆cycloalkyl, —Oaryl, -Oheteroaryl, —NHC₁-C₆alkyl,—N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂,—S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl),—C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R²;

wherein any two R¹⁰ or any two R¹¹, when on non-adjacent atoms, cancombine to form a bridging cycloalkyl or heterocyclyl;

wherein any two R¹⁰ or any two R¹¹, when on adjacent atoms, can combineto form a cycloalkyl, heterocyclyl, aryl or heteroaryl;

R¹² is independently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl),—S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl); and

n is an integer from 1 to 4.

Another aspect of the present disclosure is the provision ofpharmaceutical compositions comprising therapeutically effective amountsof at least one compound of Formula (I).

An aspect of the present disclosure concerns compounds which are, or canbe, inhibitors of one or more bromodomains of the CBP/p300 family (e.g.,compounds of Formula (I)).

An aspect of the present disclosure concerns the use of an inhibitor ofCBP/p300 family bromodomains (e.g., a compound of Formula (I)) for thepreparation of a medicament used in the treatment, prevention,inhibition or elimination of tumors (e.g., solid tumors).

An aspect of the present disclosure concerns the use of an inhibitor ofCBP/p300 family bromodomains (e.g., a compound of Formula (I)) for thepreparation of a medicament used in the treatment, prevention,inhibition or elimination of cancer. In some embodiments, the cancer isa hematological cancer such as leukemia (e.g., acute myeloid leukemia).

An aspect of the present disclosure concerns the use of an inhibitor ofCBP/p300 family bromodomains (e.g., a compound of Formula (I)) for usein the treatment, prevention, inhibition or elimination of cancer.

In some embodiments, compounds of the disclosure are of Formula (I), ora pharmaceutically acceptable salt, enantiomer, hydrate, solvate,isomer, or tautomer thereof thereof, wherein:

R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, or —OR⁵;

R² is —H, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, or aryl, wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R⁶, andwherein a —C₁-C₆alkyl group may have one or more methylene unitsreplaced by —NR⁶—, —O— or —S—;

R³ is —H, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl,heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R⁷;

R⁴ and R^(4′) are each independently —H, halogen, —OH, —CN, or —NH₂;

R⁸ is —C₁-C₆alkyl, —C₃-C₈cycloalkyl, heterocyclyl, aryl, or heteroaryl;

R⁶ and R⁷ are each independently, at each occurrence, —H, —C₁-C₆alkyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, heteroaryl, —OH, halogen, oxo, —CN,—SR⁸, —OR⁸, —(CH₂)_(n)—OR⁸, —NHR⁸, —NR⁸R⁹, —S(O)₂NR⁸R⁹, —S(O)₂R^(8′),—C(O)R^(8′), —C(O)OR⁸, —C(O)NR⁸R⁹, —NR⁸C(O)R^(9′), —NR⁸S(O)₂R^(9′),—S(O)R^(8′), —S(O)NR⁸R⁹, or —NR⁸S(O)R^(9′), wherein each alkyl,cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R¹⁰;

wherein any two R⁶ or any two R⁷, when on non-adjacent atoms, cancombine to form a bridging cycloalkyl or heterocyclyl;

wherein any two R⁶ or any two R⁷, when on adjacent atoms, can combine toform a cycloalkyl, heterocyclyl, aryl or heteroaryl;

R⁸ and R⁹ are each independently, at each occurrence, —H, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl isoptionally substituted with one or more R¹⁰ or R¹¹; or

R⁸ and R⁹ may combine with the atom to which they are both attached toform a —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰ or R¹¹;

R^(8′) and R^(9′) are each independently, at each occurrence,—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl,alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, orheteroaryl is optionally substituted with one or more R¹⁰ or R¹¹; or

R⁸ and R^(9′) may combine with the atom to which they are both attachedto form a —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰ or R¹¹;

R¹⁰ and R¹¹ are each independently, at each occurrence, —H, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂,—OC₁-C₆alkyl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl),—S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R²;

wherein any two R¹⁰ or any two R¹¹, when on non-adjacent atoms, cancombine to form a bridging cycloalkyl or heterocyclyl;

wherein any two R¹⁰ or any two R¹¹, when on adjacent atoms, can combineto form a cycloalkyl, heterocyclyl, aryl or heteroaryl;

R¹² is independently, at each occurrence, —H, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂,—OC₁-C₆alkyl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl),—S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl); and n is an integer from 1 to 4.

In some embodiments, compounds of the disclosure have the Formula (I-a):

or a pharmaceutically acceptable salt thereof, wherein Ring A representsa —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heteroaryl, or aryl and wherein each of R¹, R², R⁴,R^(4′), and R⁷ is as defined with respect to Formula (I) above anddescribed in classes and subclasses herein, both singly and incombination.

In some embodiments, compounds of the disclosure have the Formula (I-b):

or a pharmaceutically acceptable salt thereof, wherein Ring B representsa —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, oraryl and wherein each of R¹, R³, R⁴, R^(4′), and R⁶ is as defined withrespect to Formula (I) above and described in classes and subclassesherein, both singly and in combination.

In some embodiments, compounds of the disclosure have the Formula (I-c):

or a pharmaceutically acceptable salt thereof, wherein m is an integerfrom 1 to 4 and wherein each of R¹, R², R⁴, R^(4′), and R⁷ is as definedwith respect to Formula (I) above and described in classes andsubclasses herein, both singly and in combination.

In some embodiments, compounds of the disclosure have the Formula (I-d):

or a pharmaceutically acceptable salt thereof, wherein Ring B represents—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, or heteroaryl, and wherein p is aninteger from 1 to 2 and wherein each of R¹, R³, R⁴, R^(4′), and R¹⁰ isas defined with respect to Formula (I) above and described in classesand subclasses herein, both singly and in combination. In someembodiments, Ring B is —C₃-C₈cycloalkyl. In some embodiments, Ring B is—C₄-C₈cycloalkenyl. In some embodiments, Ring B is aryl. In someembodiments, Ring B is heterocyclyl. In some embodiments, Ring B isheteroaryl.

In some embodiments, compounds of the disclosure have the Formula (I-e):

or a pharmaceutically acceptable salt thereof, wherein p is 1 or 2 andwherein each of R⁶ and R⁷ is as defined with respect to Formula (I)above and described in classes and subclasses herein, both singly and incombination.

In some embodiments (e.g., embodiments of Formula I-e), p is 1. In someembodiments (e.g., embodiments of Formula I-e), p is 2. In someembodiments (e.g., embodiments of Formula I-e), R⁷ is —S(O)₂NR⁸R⁹,—C(O)OR⁸, —C(O)NR⁸R⁹, or —S(O)NR⁸R⁹. In some embodiments (e.g.,embodiments of Formula I-e), R⁷ is —S(O)₂NH₂, —C(O)OH, —C(O)NH₂, or—S(O)NH₂. In some embodiments (e.g., embodiments of Formula I-e), R⁷ is—C(O)OH. In some embodiments (e.g., embodiments of Formula I-e), R⁷ is—S(O)₂NH₂. In some embodiments (e.g., embodiments of Formula I-e), R⁷ is—C(O)NH₂. In some embodiments (e.g., embodiments of Formula I-e), R⁷ is—S(O)NH₂. In some embodiments (e.g., embodiments of Formula I-e), R⁶ isaryl or heteroaryl, wherein each aryl or heteroaryl is optionallysubstituted with one or more R¹⁰.

In some embodiments, compounds of the disclosure have the Formula (I-f):

or pharmaceutically acceptable salt thereof, wherein Ring B is—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, or heteroaryl; and L is a C₁-C₆alkylene chain optionally substituted with one or more R⁶ or L is aC₁-C₆ alkylene chain optionally substituted with one or more R⁶, andwherein at least one methylene unit of L is replaced by —NR⁶—, —O— or—S—; and wherein each of R¹, R³, R⁴, R^(4′), R⁶ and R¹⁰ is as definedwith respect to Formula (I) above and described in classes andsubclasses herein, both singly and in combination. In some embodiments,Ring B is —C₃-C₈cycloalkyl. In some embodiments, Ring B is—C₄-C₈cycloalkenyl. In some embodiments, Ring B is aryl. In someembodiments, Ring B is heterocyclyl. In some embodiments Ring B isheteroaryl. In some embodiments, L is a C₁-C₆ alkylene chain optionallysubstituted with one or more R⁶. In some embodiments, L is a C₁-C₂alkylene chain optionally substituted with one or more R⁶. In someembodiments, L is a C₁-C₆ alkylene chain optionally substituted with oneor more R⁶, and wherein at least one methylene unit is replaced by—NR⁶—, —O— or —S—. In some embodiments, L is a C₁-C₆ alkylene chainoptionally substituted with one or more R⁶, and wherein at least onemethylene unit of L is replaced by —NR⁶. In some embodiments, L is aC₁-C₆ alkylene chain optionally substituted with one or more R⁶, andwherein at least one methylene unit of L is replaced by —O—. In someembodiments, L is a C₁-C₆ alkylene chain optionally substituted with oneor more R⁶, and wherein at least one methylene unit of L is replaced by—S—. In some embodiments (e.g., embodiments of Formula I-f), L is aC₁-C₂ alkylene chain optionally substituted with R⁶ wherein R⁶ is —CH₃,—S(O)₂NH₂, —C(O)OH, —C(O)NH₂, or —S(O)NH₂. In some embodiments (e.g.,embodiments of Formula I-f), L is a C₁-C₂ alkylene chain optionallysubstituted with R⁶ wherein R⁶ is —CH₃. In some embodiments (e.g.,embodiments of Formula I-f), L is a C₁-C₂ alkylene chain optionallysubstituted with R⁶ wherein R⁶ is —S(O)₂NH₂. In some embodiments (e.g.,embodiments of Formula I-f), L is a C₁-C₂ alkylene chain optionallysubstituted with R⁶ wherein R⁶ is —C(O)OH. In some embodiments (e.g.,embodiments of Formula I-f), L is a C₁-C₂ alkylene chain optionallysubstituted with R⁶ wherein R⁶ is —C(O)NH₂. In some embodiments (e.g.,embodiments of Formula I-f), L is a C₁-C₂ alkylene chain optionallysubstituted with R⁶ wherein R⁶ is —S(O)NH₂. In some embodiments (e.g.,embodiments of Formula I-f), L is —CH₂CH(C(O)OH)—*, wherein “*” denotesthe point of attachment to Ring B. In some embodiments, R¹ is—C₁-C₆alkyl, —C₃-C₈cycloalkyl, or —OR⁵; L is —C₁-C₆alkyl, where L isoptionally substituted with one or more R⁶; Ring B is —C₃-C₈cycloalkyl,heterocyclyl, heteroaryl, or aryl; and R³ is —H, —C₁-C₆alkyl, or—C₃-C₈cycloalkyl, wherein each alkyl or cycloalkyl, is optionallysubstituted with one or more R⁷; R⁵ is methyl; R⁷ is —C₁-C₆alkyl,—C₃-C₈cycloalkyl, heterocyclyl, heteroaryl, aryl, —OH, halogen, —CN,—OR⁸, —NHR⁸, —NR⁸R⁹, —C(O)OH, —C(O)NR⁸R⁹, —S(O)CH₃, or —S(O)NR⁸R⁹; andR⁸ or R⁹ is —H or —C₁-C₆alkyl. In some embodiments R⁶ is —C(O)OH. Insome embodiments, R³ is —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, or heteroaryl. In some embodiments, R³ iscyclopentyl, cyclohexyl, 3-pyranyl, or 4-pyranyl. In some embodiments,R³ is cyclopentyl, cyclohexyl or 3-pyranyl. In some embodiments, L is anC₁-C₆ alkylene chain optionally substituted with one or more R⁶, andwherein at least one methylene unit is replaced by —NR⁶—, —O— or —S—;and R³ is —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl, orheteroaryl, wherein each —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, or heteroaryl is optionally substituted with one ormore R⁷; and R⁶ is independently, at each occurrence, —H, —C₁-C₆alkyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, heteroaryl, —OH, halogen, oxo, —CN,—SR⁸, —OR⁸, —(CH₂)_(n)—OR⁸, —NHR⁸, —NR⁸R⁹, —S(O)₂NR⁸R⁹, —S(O)₂R^(8′),—C(O)R^(8′), —C(O)NR⁸R⁹, —NR⁸C(O)R^(9′), —NR⁸S(O)₂R^(9′), —S(O)R^(8′),—S(O)NR⁸R⁹, or —NR⁸S(O)R^(9′), wherein each alkyl, cycloalkyl,heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more R¹⁰, wherein R¹⁰ is —H,—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, halogen, —NO₂, —CN,—NH₂, —OC₁-C₆alkyl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl,—C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂,—C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl),—S(O)N(C₁-C₆alkyl)₂, or —N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more —R¹². Insome embodiments, L is a C₁-C₆ alkylene chain, —OCH₂—, —CH₂O—, —NR⁶CH₂—,or —CH₂NR⁶—; and R⁶ is H, —C₁-C₆alkyl, —C₃-C₆cycloalkyl or —C(O)NR⁸R⁹.In some embodiments, R³ is cyclopentyl or cyclohexyl, wherein eachcyclopentyl or cyclohexyl is optionally substituted with R⁷. In someembodiments, R³ is cyclopentyl or cyclohexyl, wherein each cyclopentylor cyclohexyl is optionally substituted with R⁷, wherein R⁷ is —OH,halogen, oxo, —CN, —SH, —OH, —NH₂, —S(O)₂NH₂, —C(O)OH, or —C(O)NH₂.

In some embodiments, compounds of the disclosure have the Formula (I-g)

-   -   or a pharmaceutically acceptable salt thereof, wherein each of        R¹, R³, R⁴, R^(4′),R⁶, Ring B and R¹⁰ is as defined with respect        to Formula (I) above and described in classes and subclasses        herein, both singly and in combination.

In some embodiments, compounds of the disclosure have the Formula (I-h)

-   -   or a pharmaceutically acceptable salt thereof, wherein each of        R¹, R⁴, R^(4′), R⁶, and R⁷ is as defined with respect to        Formula (I) above and described in classes and subclasses        herein, both singly and in combination.

In some embodiments, compounds of the disclosure have the Formula (I-h′)

-   -   or a pharmaceutically acceptable salt thereof, wherein each of        R¹, R⁴, R^(4′), R⁶, and R⁷ is as defined with respect to        Formula (I) above and described in classes and subclasses        herein, both singly and in combination.

In some embodiments, compounds of the disclosure have the Formula (I-h″)

-   -   or a pharmaceutically acceptable salt thereof, wherein each of        R¹, R⁴, R^(4′), R⁶, and R⁷ is as defined with respect to        Formula (I) above and described in classes and subclasses        herein, both singly and in combination.

In some embodiments, compounds of the disclosure have the Formula (I-i):

-   -   or a pharmaceutically acceptable salt thereof,

wherein,

R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, —OR⁵, —N(R⁵)₂, or—NHR⁵;

R⁵ is —C₁-C₆alkyl, —C₃-C₈cycloalkyl, heterocyclyl, aryl, or heteroaryl;

each R⁶ is —OH, halogen, oxo, —C₁-C₆alkyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl,spiroheterocyclyl, heteroaryl, —NO₂, —CN, —NH₂, —(CH₂)_(n)—OR⁸,—C(O)R^(8′), —C(O)OR⁸, or —C(O)NR⁸R⁹, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, cycloalkyl,heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more R¹⁰;

R^(6′) is H or —C₁-C₆alkyl;

R⁷ is independently, at each occurrence, —H, halogen, —OH, —CN,—OC₁-C₆alkyl, —NH₂, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —S(O)₂₀H,—C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂,—C(O)OH, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, —S(O)₂NH₂,—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl) or tetrazole;

R⁸ and R⁹ are each independently, at each occurrence, —H, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl isoptionally substituted with one or more R¹⁰; or

R⁸ and R⁹ may combine with the atom to which they are both attached toform a spiroheterocyclyl, heterocyclyl, or heteroaryl, wherein theformed spiroheterocyclyl, heterocyclyl,or heteroaryl is optionallysubstituted with one or more R¹⁰;

R^(8′) is each independently, at each occurrence, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl isoptionally substituted with one or more R¹⁰; or R¹⁰ is independently, ateach occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl,—OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl, —OC₃-C₆cycloalkyl,-Oaryl, -Oheteroaryl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl,—C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl), —NHC(O)C₁-C₆alkyl,—C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R¹²;

wherein any two R¹⁰ when on non-adjacent atoms, can combine to form abridging cycloalkyl or heterocyclyl;

wherein any two R¹⁰ when on adjacent atoms, can combine to form acycloalkyl, heterocyclyl, aryl or heteroaryl;

R¹² is independently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl),—S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl); and

m is an integer from 0 to 5;

n is an integer from 1 to 4; and

q is an integer from 0 to 4.

In some embodiments, compounds of the disclosure have the Formula (I-j):

or a pharmaceutically acceptable salt thereof,

wherein:

R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, —OR⁵, —N(R⁵)₂, or—NHR⁵;

R⁵ is independently, at each occurrence, —C₁-C₆alkyl, —C₃-C₈cycloalkyl,heterocyclyl, aryl, or heteroaryl;

R⁶ is —C₁-C₆alkyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, halogen, oxo,—(CH₂)_(n)—OR, —C(O)R^(8′), —C(O)OR⁸, or —C(O)NR⁸R⁹, wherein each alkyl,cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R¹⁰;

R⁸ and R⁹ are each independently, at each occurrence, —H, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl isoptionally substituted with one or more R¹⁰ or R¹¹; or

R⁸ and R⁹ may combine with the atom to which they are both attached toform a spiroheterocyclyl, heterocyclyl, or heteroaryl, wherein theformed spiroheterocyclyl, heterocyclyl,or heteroaryl is optionallysubstituted with one or more R¹⁰ or R¹¹;

R^(8′) is each independently, at each occurrence, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl isoptionally substituted with one or more R¹⁰ or R¹¹;

R¹⁰ is each independently, at each occurrence, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂,—OC₁-C₆alkyl, —OC₃-C₆cycloalkyl, -Oaryl, -Oheteroaryl, —NHC₁-C₆alkyl,—N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂,—S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl),—C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R¹²;

wherein any two R¹⁰ when on non-adjacent atoms, can combine to form abridging cycloalkyl or heterocyclyl;

wherein any two R¹⁰ when on adjacent atoms, can combine to form acycloalkyl, heterocyclyl, aryl or heteroaryl;

R¹² is independently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl),—S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl); and

n is an integer from 1 to 4.

In some embodiments, for compounds of Formula (I-j) or apharmaceutically acceptable salt thereof:

R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, —OR⁵, —N(R⁵)₂, or—NHR⁵;

R⁵ is —C₁-C₆alkyl, —C₃-C₈cycloalkyl, heterocyclyl, aryl, or heteroaryl;

R⁶ is —C₁-C₆alkyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, halogen, oxo,—(CH₂)_(n)—OR, —C(O)R^(8′), —C(O)OR⁸, or —C(O)NR⁸R⁹, wherein each alkyl,cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R¹⁰;

R⁸ and R⁹ are each independently, at each occurrence, —H, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl isoptionally substituted with one or more R¹⁰ or R¹¹; or

R⁸ and R⁹ may combine with the atom to which they are both attached toform a spiroheterocyclyl, heterocyclyl, or heteroaryl, wherein theformed spiroheterocyclyl, heterocyclyl,or heteroaryl is optionallysubstituted with one or more R¹⁰ or R¹¹;

R^(8′) is each independently, at each occurrence, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl isoptionally substituted with one or more R¹⁰ or R¹¹; or

R¹⁰ is each independently, at each occurrence, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂,—OC₁-C₆alkyl, —OC₃-C₆cycloalkyl, -Oaryl, -Oheteroaryl, —NHC₁-C₆alkyl,—N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂,—S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl),—C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R¹².

wherein any two R¹⁰ when on non-adjacent atoms, can combine to form abridging cycloalkyl or heterocyclyl;

wherein any two R¹⁰ when on adjacent atoms, can combine to form acycloalkyl, heterocyclyl, aryl or heteroaryl;

R¹² is independently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl),—S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl); and

n is an integer from 1 to 4.

In some embodiments, compounds of the disclosure have the Formula (I-k):

-   -   or a pharmaceutically acceptable salt thereof,

wherein,

R¹ is —OR⁵;

R⁵ is —C₁-C₆alkyl;

R⁶ is —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl,aryl, wherein each cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl,or aryl is optionally substituted with one or more —R¹⁰;

R⁷ is —H, halogen, —OH, —CN, —OC₁-C₆alkyl, —NH₂, —NHC₁-C₆alkyl,—N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂,—S(O)₂C₁-C₆alkyl, —S(O)₂₀H, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OH, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂,—S(O)₂NH₂, —N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl) or tetrazole;

R¹⁰ is independently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—OC₃-C₆cycloalkyl, -Oaryl, -Oheteroaryl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl,—C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl), —NHC(O)C₁-C₆alkyl,—C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R¹²;

each R¹² is independently halogen;

m is an integer from 0 to 5.

In some embodiments, compounds of the disclosure have the Formula (I-l):

-   -   or a pharmaceutically acceptable salt thereof,

wherein,

R¹ is —OR⁵;

R⁵ is —C₁-C₆alkyl;

R⁶ is —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—OC₃-C₆cycloalkyl, -Oaryl, -Oheteroaryl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl,—C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂,—C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl),—S(O)N(C₁-C₆alkyl)₂, or —N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more —R¹⁰;

R⁷ is independently, at each occurrence, —H, halogen, —OH, —CN,—OC₁-C₆alkyl, —NH₂, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —S(O)₂₀H,—C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂,—C(O)OH, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, —S(O)₂NH₂,—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl) or tetrazole;

R¹⁰ is independently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—OC₃-C₆cycloalkyl, -Oaryl, -Oheteroaryl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl,—C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl), —NHC(O)C₁-C₆alkyl,—C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R¹²;

each R¹² is independently halogen;

m is an integer from 0 to 5; and

r is an integer from 0 to 5.

In some embodiments, compounds of the disclosure have the Formula (I-m)

or a pharmaceutically acceptable salt, thereof,

wherein:

R¹ is —OR⁵;

R⁵ is —C₁-C₆alkyl;

R⁶ is phenyl optionally substituted with one or more R¹⁰;

R¹⁰ is each independently, at each occurrence, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂,—OC₁-C₆alkyl, —OC₃-C₆cycloalkyl, -Oaryl, -Oheteroaryl, —NHC₁-C₆alkyl,—N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂,—S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl),—C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R¹²;

wherein any two R¹⁰ when on non-adjacent atoms, can combine to form abridging cycloalkyl or heterocyclyl;

wherein any two R¹⁰ when on adjacent atoms, can combine to form acycloalkyl, heterocyclyl, aryl or heteroaryl;

R¹² is independently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl),—S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl); and

n is an integer from 1 to 4.

In some embodiments, compounds of the disclosure have the Formula (I-n)

or a pharmaceutically acceptable salt thereof,

wherein:

R¹ is —OR⁵;

R⁵ is —C₁-C₃alkyl;

R⁶ is phenyl optionally substituted with one or more R¹⁰;

R¹⁰ is independently, at each occurrence halogen, —OC₁-C₆alkyl,—OC₃-C₆cycloalkyl, -Oaryl, or -Oheteroaryl, wherein each alkyl,cycloalkyl, aryl or heteroaryl is optionally substituted with one ormore —R¹²;

R¹² is independently halogen.

In some embodiments, for compounds of Formula (I-n), or apharmaceutically acceptable salt thereof:

R¹ is —OR⁵;

R⁵ is —C₁-C₃alkyl;

R⁶ is phenyl optionally substituted with one or more R¹⁰;

R¹⁰ is independently, at each occurrence halogen, —OC₁-C₆alkyl,—OC₃-C₆cycloalkyl, -Oaryl, or -Oheteroaryl, wherein each alkyl,cycloalkyl, aryl or heteroaryl is optionally substituted with one ormore —R¹²;

R¹² is halogen.

It will be appreciated that throughout the present disclosure, unlessotherwise indicated, reference to a compound of Formula (I) is intendedto also include formulae (I-a), (I-b), (I-c), (I-d), (I-e), (I-f),(I-g), (I-h), (I-h′), (I-h″), (I-i), (I-j), (I-k), (I-l), (I-m), and(I-n) and compound species of such formulae disclosed herein.

In some embodiments, R¹ is —OCR⁵.

Compounds of the present disclosure can be compounds wherein R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, —OR⁵, —N(R⁵)₂, or—NHR⁵. Compounds of the present disclosure can be compounds wherein R¹is —OR⁵. Compounds of the present disclosure can be compounds wherein R¹is —OR⁵ and R⁵ is methyl.

Compounds of the present disclosure can be compounds wherein R⁵ is—C₁-C₆alkyl, —C₃-C₈cycloalkyl, heterocyclyl, aryl, or heteroaryl.Compounds of the present disclosure can be compounds wherein R⁵ is—C₁-C₆alkyl. Compounds of the present disclosure can be compoundswherein R⁵ is —C₁-C₃alkyl. Compounds of the present disclosure can becompounds wherein R⁵ is methyl.

Compounds of the present disclosure can be compounds wherein R⁶ is—C₁-C₆alkyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, heteroaryl, halogen, oxo,—(CH₂)_(n)—OR⁸, —C(O)R^(8′), —C(O)OR⁸, or —C(O)NR⁸R⁹, wherein eachalkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R¹⁰.Compounds of the present disclosure can be compounds wherein R⁶ is—C₃-C₈cycloalkyl, heterocyclyl, aryl, spirocycloalkyl,spiroheterocyclyl, or heteroaryl, wherein each cycloalkyl, heterocyclyl,spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰. Compounds of the present disclosurecan be compounds wherein R⁶ is aryl optionally substituted with one ormore R¹⁰. Compounds of the present disclosure can be compounds whereinR⁶ is phenyl optionally substituted with one or more R¹⁰. Compounds ofthe present disclosure can be compounds wherein R⁶ is phenyl substitutedwith one R¹⁰. Compounds of the present disclosure can be compoundswherein R⁶ is phenyl substituted with two R¹⁰.

Compounds of the present disclosure can be compounds wherein R¹⁰ isindependently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—OC₃-C₆cycloalkyl, -Oaryl, -Oheteroaryl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl,—C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂,—C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl),—S(O)N(C₁-C₆alkyl)₂, or —N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more —R¹².Compounds of the present disclosure can be compounds wherein R¹⁰ isindependently, at each occurrence, —C₁-C₆alkyl, —C₃-C₈cycloalkyl,heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, CN, —OC₁-C₆alkyl,—OC₃-C₆cycloalkyl, or —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂ wherein each alkyl,cycloalkyl, heterocyclyl, heteroaryl, or aryl is optionally substitutedwith one or more —R¹². Compounds of the present disclosure can becompounds wherein R¹⁰ is independently, at each occurrence, —C₁-C₆alkyl,—OC₁-C₆alkyl, —OC₃-C₆cycloalkyl, or halogen wherein each alkyl, orcycloalkyl, is optionally substituted with one or more —R¹² Compounds ofthe present disclosure can be compounds wherein R¹⁰ is independently, ateach occurrence, —OC₁-C₆alkyl, or halogen wherein each alkyl isoptionally substituted with one or more —R¹².

Compounds of the present disclosure can be compounds wherein R¹² isindependently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl),—S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl). Compounds of the present disclosure canbe compounds wherein R¹² is independently, at each occurrence, halogen.Compounds of the present disclosure can be compounds wherein R¹² isfluoro. Compounds of the present disclosure can be compounds wherein R¹²is chloro.

Compounds of the present disclosure can be compounds wherein R¹ is —OR⁵;R⁵ is —C₁-C₆alkyl; R⁶ is —C₃-C₈cycloalkyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, or heteroaryl, wherein eachcycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R¹⁰; R¹⁰is independently, at each occurrence, —C₁-C₆alkyl, —OC₁-C₆alkyl,—OC₃-C₆cycloalkyl, or halogen wherein each alkyl, or cycloalkyl, isoptionally substituted with one or more —R¹² and —R¹² is halogen.

Compounds of the present disclosure can be compounds wherein R¹ is —OR⁵;R⁵ is —C₁-C₃alkyl; R⁶ is aryl optionally substituted with one or moreR¹⁰; R¹⁰ is independently, at each occurrence, —C₁-C₆alkyl,—OC₁-C₆alkyl, —OC₃-C₆cycloalkyl, or halogen wherein each alkyl, orcycloalkyl, is optionally substituted with one or more —R¹² and —R¹² ishalogen.

Compounds of the present disclosure can be compounds wherein R¹ is —OR⁵;R⁵ is —C₁-C₃alkyl; R⁶ is aryl substituted with one R¹⁰; R¹⁰ is—C₁-C₆alkyl, —OC₁-C₆alkyl, —OC₃-C₆cycloalkyl, or halogen wherein eachalkyl, or cycloalkyl, is optionally substituted with one or more —R¹²and —R¹² is halogen.

Compounds of the present disclosure can be compounds wherein R¹ is —OR⁵;R⁵ is —C₁-C₃alkyl; R⁶ is aryl substituted with two R¹⁰; R¹⁰ isindependently, at each occurrence, —OC₁-C₆alkyl or halogen wherein eachalkyl is optionally substituted with one or more —R¹² and —R¹² ishalogen.

Compounds of the present disclosure can be compounds wherein R¹ is —OR⁵;R⁵ is methyl; R⁶ is phenyl substituted with two R¹⁰; R¹⁰ isindependently, at each occurrence, —OC₁-C₆alkyl or halogen wherein eachalkyl is optionally substituted with one or more —R¹² and —R¹² ishalogen.

Compounds of the present disclosure can be compounds wherein R¹ is —OR⁵;R⁵ is methyl; and R⁶ is phenyl.

Compounds of the present disclosure can be compounds wherein R⁶ is aryl,optionally substituted with one or two R¹⁰, wherein R¹⁰ isindependently, at each occurrence, halogen or —OC₁-C₆alkyl, wherein—OC₁-C₆alkyl is optionally substituted with halogen.

Compounds of the present disclosure can comprise aryl, wherein aryl canbe ring systems having a total of five to fourteen ring members, whereinat least one ring in the system is aromatic and wherein each ring in thesystem contains 3 to 7 ring members. For example, aryl can include, butis not limited to, phenyl.

Compounds of the present disclosure can comprise heteroaryl, whereinheteroaryl is a group having 5 to 10 ring atoms, preferably 5, 6, or 9ring atoms; having 6, 10, or 14π electrons shared in a cyclic array;and/or having, in addition to carbon atoms, from one to five heteroatomswherein the term “heteroatom” refers to nitrogen, oxygen, or sulfur, andincludes any oxidized form of nitrogen or sulfur, and any quaternizedform of a basic nitrogen. For example, heteroaryl can include, but areis not limited to, pyridine, indole, benzapyrazole, benzoxale,furopyridine, or isoquinoline.

Compounds of the present disclosure can comprise heterocyclyl, whereinheterocyclyl is a stable 5- to 7-membered monocyclic or 7-10-memberedbicyclic heterocyclic moiety that is either saturated or partiallyunsaturated, and having, in addition to carbon atoms, one or more,preferably one to four, heteroatoms, as defined above. For example,heterocyclyl can include, but are is not limited to, dihydrofuran,dihydrofuropyrine or dihydroisofuran.

In some embodiments, R¹ is —OR⁵, —N(R⁵)₂, —NHR⁵, or —C₁-C₆alkyl. In someembodiments, R¹ is —OR⁵ or —C₁-C₆alkyl. In some embodiments, R⁵ of R¹ is—C₁-C₆alkyl. In some embodiments, R¹ is —OCH₃. In some embodiments, R¹is —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, heteroaryl, or aryl. In some embodiments, R¹ is—C₁-C₆alkyl. In some embodiments, R¹ is methyl, ethyl or propyl. In someembodiments, R¹ is methyl. In some embodiments, R¹ is —C₂-C₆alkenyl. Insome embodiments, R¹ is aryl.

In some embodiments, R² is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, or aryl,wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,heterocyclyl, heteroaryl, or aryl is optionally substituted with one ormore R⁶. In some embodiments, R² is —H. In some embodiments, R² isC₁-C₆alkyl optionally substituted with one or more R⁶. In someembodiments, R² is aryl optionally substituted with one or more R⁶. Insome embodiments, R² is C₃-C₈cycloalkyl optionally substituted with oneor more R⁶. In some embodiments, R² is C₁-C₂alkyl substituted with arylor heteroaryl, wherein each aryl or heteroaryl is optionally substitutedwith one or more R¹⁰. In some embodiments R² is methyl optionallysubstituted with one or more R⁶. In some embodiments R² is ethyloptionally substituted with one or more R⁶. In some embodiments, R² isC₁-C₂alkyl substituted with aryl or heteroaryl, wherein each aryl orheteroaryl is optionally substituted with one or more R¹⁰, and whereinR³ is cyclohexyl optionally substituted with one or more —C(O)OH.

In some embodiments, R³ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R⁷. In some embodiments, R³ or R^(3′) is—H. In some embodiments, R³ is —C₁-C₆alkyl. In some embodiments, R³ isheterocyclyl optionally substituted with one or more R⁷. In someembodiments, R³ is heteroaryl optionally substituted with one or moreR⁷. In some embodiments, R³ is spirocycloalkyl optionally substitutedwith one or more R⁷. In some embodiments, R³ is spiroheterocyclyloptionally substituted with one or more R⁷. In some embodiments, R³ isC₃-C₈cycloalkyl optionally substituted with one or more R⁷. In someembodiments, R³ is aryl optionally substituted with one or more R⁷. Insome embodiments, R³ is cyclohexyl optionally substituted with one ormore —R⁷. In some embodiments, R³ is cyclohexyl optionally substitutedwith one or more —C(O)OH.

In some embodiments, R³ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R⁷. In some embodiments, R³ is —H. In someembodiments, R³ is —C₁-C₆alkyl. In some embodiments, R³ is heterocyclyloptionally substituted with one or more R⁷. In some embodiments, R³ iscyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl optionallysubstituted with one or more R⁷. In some embodiments, R³ is cyclopropyloptionally substituted with one or more R⁷. In some embodiments, R³ iscyclobutyl optionally substituted with one or more R⁷. In someembodiments, R³ is cyclopentyl optionally substituted with one or moreR⁷. In some embodiments, R³ is cyclohexyl optionally substituted withone or more R⁷. In some embodiments, R³ is heteroaryl optionallysubstituted with one or more R⁷. In some embodiments, R³ isspirocycloalkyl optionally substituted with one or more R⁷. In someembodiments, R³ is spiroheterocyclyl optionally substituted with one ormore R⁷. In some embodiments, R³ is C₃-C₈cycloalkyl optionallysubstituted with one or more R⁷. In some embodiments, R³ is aryloptionally substituted with one or more R⁷. In some embodiments, R³ iscyclohexyl optionally substituted with one or more —R⁷. In someembodiments, R³ is cyclohexyl optionally substituted with one or more—C(O)OH.

In some embodiments, R⁴ and R^(4′) are independently hydrogen, halogen,—OH, —CN, or —NH₂. In some embodiments, R⁴ and R^(4′) are —H. In someembodiments, R⁴ and R^(4′) are halogen.

In some embodiments, R⁵ is —C₁-C₆alkyl, —C₃-C₈cycloalkyl, heterocyclyl,aryl, or heteroaryl. In some embodiments, R⁵ is —C₁-C₆alkyl. In someembodiments, R⁵ is —C₁-C₃alkyl. In some embodiments, R⁵ is methyl. Insome embodiments, R⁵ is ethyl.

In some embodiments, R⁶ is —C₁-C₆alkyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl,spiroheterocyclyl, heteroaryl, —OH, halogen, oxo, —CN, —SR⁸, —OR⁸,—(CH₂)_(n)—OR⁸, —NHR⁸, —NR⁸R⁹, —S(O)₂NR⁸R⁹, —S(O)₂R^(8′), —C(O)R^(8′),—C(O)OR⁸, —C(O)NR⁸R⁹, —NR⁸C(O)R^(9′), —NR⁸S(O)₂R^(9′), —S(O)R^(8′),—S(O)NR⁸R⁹, or —NR⁸S(O)R⁹, wherein each alkyl, cycloalkyl, heterocyclyl,spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰. In some embodiments, R⁶ is—C₁-C₆alkyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, oraryl. In some embodiments, R⁶ is —C₁-C₆alkyl optionally substituted withone or more R¹⁰. In some embodiments, R⁶ is aryl optionally substitutedwith one or more R¹⁰. In some embodiments, R⁶ is heteroaryl optionallysubstituted with one or more R¹⁰. In some embodiments, R⁶ is —C(O)OH. Insome embodiments, R⁶ is halogen. In some embodiments, R⁶ is —C₁-C₆alkyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, heteroaryl, halogen, oxo,—(CH₂)_(n)—OR⁸, —C(O)R^(8′), —C(O)OR⁸, or —C(O)NR⁸R⁹, wherein eachalkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R¹⁰.

In some embodiments, R⁷ is —C₁-C₆alkyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl,spiroheterocyclyl, heteroaryl, —OH, halogen, oxo, —CN, —SR⁸, —OR⁸,—(CH₂)_(n)—OR⁸, —NHR⁸, —NR⁸R⁹, —S(O)₂NR⁸R⁹, —S(O)₂R^(8′), —C(O)R^(8′),—C(O)OR⁸, —C(O)NR⁸R⁹, —NR⁸C(O)R^(9′), —NR⁸S(O)₂R^(9′), —S(O)R^(8′),—S(O)NR⁸R⁹, or —NR⁸S(O)R^(9′), wherein each alkyl, cycloalkyl,heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more R¹⁰. In some embodiments, R⁷ is—C₁-C₆alkyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, oraryl. In some embodiments R⁷ is —C₁-C₆alkyl optionally substituted withone or more R¹⁰. In some embodiments, R⁷ is aryl optionally substitutedwith one or more R¹⁰. In some embodiments, R⁷ is heteroaryl optionallysubstituted with one or more R¹⁰. In some embodiments, R⁷ is —C(O)OH. Insome embodiments, R⁷ is halogen.

In some embodiments, R⁸ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl, heteroaryl,wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,heterocyclyl, aryl, or heteroaryl is optionally substituted with one ormore R¹⁰ or R¹¹. In some embodiments, R⁸ is —H. In some embodiments, R⁸is —C₁-C₆alkyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, oraryl, wherein R⁸ is optionally substituted with R¹⁰ or R¹¹. In someembodiments, R⁸ is —C₁-C₆alkyl optionally substituted with one or moreR¹⁰ or R¹¹. In some embodiments, R⁸ is aryl optionally substituted withone or more R¹⁰ or R¹¹. In some embodiments, R⁸ is heteroaryl optionallysubstituted with one or more R¹⁰ or R¹¹.

In some embodiments, R^(8′) is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionallysubstituted with one or more R¹⁰ or R¹¹. In some embodiments, R^(8′) is—C₁-C₆alkyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, oraryl, wherein R^(8′) is optionally substituted with R¹⁰ or R¹¹. In someembodiments, R^(8′) is —C₁-C₆alkyl optionally substituted with one ormore R¹⁰ or R¹¹. In some embodiments, R^(8′) is aryl optionallysubstituted with one or more R¹⁰ or R¹¹. In some embodiments, R^(8′) isheteroaryl optionally substituted with one or more R¹⁰ or R¹¹.

In some embodiments, R⁹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl, heteroaryl,wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,heterocyclyl, aryl, or heteroaryl is optionally substituted with one ormore R¹⁰ or R¹¹. In some embodiments, R⁹ is —H. In some embodiments, R⁹is —C₁-C₆alkyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, oraryl, wherein R⁹ is optionally substituted with R¹⁰ or R¹¹. In someembodiments, R⁹ is —C₁-C₆alkyl optionally substituted with one or moreR¹⁰ or R¹¹. In some embodiments, R⁹ is aryl optionally substituted withone or more R¹⁰ or R¹¹. In some embodiments, R⁹ is heteroaryl optionallysubstituted with one or more R¹⁰ or R¹¹.

In some embodiments, R^(9′) is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionallysubstituted with one or more R¹⁰ or R¹¹. In some embodiments, R^(9′) is—C₁-C₆alkyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, oraryl, wherein R^(9′) is optionally substituted with R¹⁰ or R¹¹. In someembodiments, R^(9′) is —C₁-C₆alkyl optionally substituted with one ormore R¹⁰ or R¹¹. In some embodiments, R^(9′) is aryl optionallysubstituted with one or more R¹⁰ or R¹¹. In some embodiments, R^(9′) isheteroaryl optionally substituted with one or more R¹⁰ or R¹¹.

In some embodiments, R¹⁰ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl,—OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl, —NHC₁-C₆alkyl,—N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂,—S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl),—C(O)N(C₁-C₆alkyl)₂, —C(O)OC-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R¹². In some embodiments, R¹⁰is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, wherein R¹⁰ issubstituted with R¹². In some embodiments, R¹⁰ is halogen. In someembodiments, R¹⁰ is each independently, at each occurrence, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂,—OC₁-C₆alkyl, —OC₃-C₆cycloalkyl, Oaryl, Oheteroaryl, —NHC₁-C₆alkyl,—N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂,—S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl),—C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R¹²; wherein any two R¹⁰ whenon non-adjacent atoms, can combine to form a bridging cycloalkyl orheterocyclyl; wherein any two R¹⁰ when on adjacent atoms, can combine toform a cycloalkyl, heterocyclyl, aryl or heteroaryl. In someembodiments, R¹⁰ is each independently, at each occurrence halogen or—OC₁-C₆alkyl, —OC₃-C₆cycloalkyl, Oaryl, Oheteroaryl, wherein each alkyl,cycloalkyl, aryl or heteroaryl is optionally substituted with one ormore —R¹².

In some embodiments, R¹¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl,—OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl, —NHC₁-C₆alkyl,—N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂,—S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl),—C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R¹². In some embodiments, R¹¹is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, wherein R¹¹ issubstituted with R¹². In some embodiments, R¹¹ is halogen.

In some embodiments, R¹² is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl,—OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl, —NHC₁-C₆alkyl,—N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂,—S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl),—C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl). In some embodiments, R¹² is —H. In someembodiments, R¹² is halogen.

In some embodiments, n is 1. In some embodiments, n is 2. In someembodiments, n is 3. In some embodiments, n is 4.

In some embodiments R¹ is —C₁-C₆alkyl, —C₃-C₈cycloalkyl, or —OR⁵; R² is—C₁-C₆alkyl, —C₃-C₈cycloalkyl, heterocyclyl, heteroaryl, or aryl,wherein each alkyl, cycloalkyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more R⁶; R³ is —H, —C₁-C₆alkyl, or—C₃-C₈cycloalkyl, wherein each alkyl, or cycloalkyl is optionallysubstituted with one or more R⁷; R⁵ is methyl; R⁷ is-C₁-C₆alkyl,—C₃-C₈cycloalkyl, heterocyclyl, heteroaryl, aryl, —OH, halogen, —CN,—OR⁸, —NHR⁸, —NR⁸R⁹, —C(O)OH, —C(O)NR⁸R⁹, —S(O)CH₃, or —S(O)NR⁸R⁹; andR⁸ or R⁹ is —H, or —C₁-C₆alkyl.

In some embodiments R¹ is —C₁-C₆alkyl, —C₃-C₈cycloalkyl, or —OR⁵; and R²is (—CH₂)₁₋₂cycloalkyl, (—CH₂)₁₋₂heterocyclyl, (—CH₂)₁₋₂heteroaryl, or(—CH₂)₁₋₂aryl wherein each alkyl, cycloalkyl, heterocyclyl, heteroaryl,or aryl is optionally substituted with one or more R⁶; and R³ is(—CH₂)₁₋₂cycloalkyl, (—CH₂)₁₋₂heterocyclyl, (—CH₂)₁₋₂heteroaryl, or(—CH₂)₁₋₂aryl wherein each alkyl, cycloalkyl, heterocyclyl, heteroaryl,or aryl is optionally substituted with one or more R⁷; and R⁵ is methyl;and R⁷ is-C₁-C₆alkyl, —C₃-C₈cycloalkyl, heterocyclyl, heteroaryl, aryl,—OH, halogen, —CN, —OR⁸, —NHR⁸, —NR⁸R⁹, —C(O)OH, —C(O)NR⁸R⁹, —S(O)CH₃,or —S(O)NR⁸R⁹; and R⁸ or R⁹ is —H, or —C₁-C₆alkyl.

In some embodiments, R¹ is —OR⁵ and R² is alkyl. In some embodiments, R¹is —OR⁵ and R² is cycloalkyl. In some embodiments, R¹ is —OR⁵ and R² isaryl. In some embodiments, R¹ is —OR⁵ and R² is heteroaryl. In someembodiments, R¹ is —OR⁵ and R² is alkyl substituted with cycloalkyl. Insome embodiments, R¹ is —OR⁵ and R² is alkyl substituted withheterocycloalkyl. In some embodiments, R¹ is —OR⁵ and R² is alkylsubstituted with aryl. In some embodiments, R¹ is —OR⁵ and R² is alkylsubstituted with heteroaryl.

In some embodiments, R¹ is —OR⁵, R² is alkyl, and R³ is alkyl. In someembodiments, R¹ is —OR⁵, R² is cycloalkyl, and R³ is alkyl. In someembodiments, R¹ is —OR⁵, R² is aryl, and R³ is alkyl. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, and R³ is alkyl. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with cycloalkyl, and R³is alkyl. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, and R³ is alkyl. In some embodiments, R¹ is —OR⁵, R²is alkyl substituted with aryl, and R³ is alkyl. In some embodiments, R¹is —OR⁵, R² is alkyl substituted with heteroaryl, and R³ is alkyl.

In some embodiments, R¹ is —OR⁵, R² is alkyl, and R³ is cycloalkyl. Insome embodiments, R¹ is —OR⁵, R² is cycloalkyl, and R³ is cycloalkyl. Insome embodiments, R¹ is —OR⁵, R² is aryl, and R³ is cycloalkyl. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, and R³ is cycloalkyl. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with cycloalkyl, and R³is cycloalkyl. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heterocycloalkyl, and R³ is cycloalkyl. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, and R³ is cycloalkyl. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heteroaryl, and R³is cycloalkyl.

In some embodiments, R¹ is —OR⁵, R² is alkyl, and R³ is aryl. In someembodiments, R¹ is —OR⁵, R² is cycloalkyl, and R³ is aryl. In someembodiments, R¹ is —OR⁵, R² is aryl, and R³ is aryl. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, and R³ is aryl. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with cycloalkyl, and R³is aryl. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, and R³ is aryl. In some embodiments, R¹ is —OR⁵, R² isalkyl substituted with aryl, and R³ is aryl. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with heteroaryl, and R³ is aryl.

In some embodiments, R¹ is —OR⁵, R² is alkyl, and R³ is heteroaryl. Insome embodiments, R¹ is —OR⁵, R² is cycloalkyl, and R³ is heteroaryl. Insome embodiments, R¹ is —OR⁵, R² is aryl, and R³ is heteroaryl. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, and R³ is heteroaryl. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with cycloalkyl, and R³is heteroaryl. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heterocycloalkyl, and R³ is heteroaryl. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, and R³ is heteroaryl. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heteroaryl, and R³is heteroaryl.

In some embodiments, R¹ is —OR⁵, R² is alkyl, and R³ is alkylsubstituted with cycloalkyl. In some embodiments, R¹ is —OR⁵, R² iscycloalkyl, and R³ is alkyl substituted with cycloalkyl. In someembodiments, R¹ is —OR⁵, R² is aryl, and R³ is alkyl substituted withcycloalkyl. In some embodiments, R¹ is —OR⁵, R² is heteroaryl, and R³ isalkyl substituted with cycloalkyl. In some embodiments, R¹ is —OR⁵, R²is alkyl substituted with cycloalkyl, and R³ is alkyl substituted withcycloalkyl. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heterocycloalkyl, and R³ is alkyl substituted with cycloalkyl. Insome embodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, and R³is alkyl substituted with cycloalkyl. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, and R³ is alkyl substitutedwith cycloalkyl.

In some embodiments, R¹ is —OR⁵, R² is alkyl, and R³ is alkylsubstituted with aryl. In some embodiments, R¹ is —OR⁵, R² iscycloalkyl, and R³ is alkyl substituted with aryl. In some embodiments,R¹ is —OR⁵, R² is aryl, and R³ is alkyl substituted with aryl. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, and R³ is alkyl substitutedwith aryl. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withcycloalkyl, and R³ is alkyl substituted with aryl. In some embodiments,R¹ is —OR⁵, R² is alkyl substituted with heterocycloalkyl, and R³ isalkyl substituted with aryl. In some embodiments, R¹ is —OR⁵, R² isalkyl substituted with aryl, and R³ is alkyl substituted with aryl. Insome embodiments, R¹ is —OR⁵, R² is alkyl substituted with heteroaryl,and R³ is alkyl substituted with aryl.

In some embodiments, R¹ is —OR⁵, R² is alkyl, and R³ is alkylsubstituted with heteroaryl. In some embodiments, R¹ is —OR⁵, R² iscycloalkyl, and R³ is alkyl substituted with heteroaryl. In someembodiments, R¹ is —OR⁵, R² is aryl, and R³ is alkyl substituted withheteroaryl. In some embodiments, R¹ is —OR⁵, R² is heteroaryl, and R³ isalkyl substituted with heteroaryl. In some embodiments, R¹ is —OR⁵, R²is alkyl substituted with cycloalkyl, and R³ is alkyl substituted withheteroaryl. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heterocycloalkyl, and R³ is alkyl substituted with heteroaryl. Insome embodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, and R³is alkyl substituted with heteroaryl. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, and R³ is alkyl substitutedwith heteroaryl.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isalkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² isaryl, R³ is alkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is heteroaryl, R³ is alkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with cycloalkyl, R³ isalkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² isalkyl substituted with heterocycloalkyl, R³ is alkyl, and R⁴ and R^(4′)are —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted witharyl, R³ is alkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with heteroaryl, R³ is alkyl, and R⁴ andR^(4′) are —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is cycloalkyl, and R⁴and R^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³is cycloalkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is aryl, R³ is cycloalkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is cycloalkyl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith cycloalkyl, R³ is cycloalkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heterocycloalkyl,R³ is cycloalkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is cycloalkyl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is cycloalkyl, and R⁴ and R^(4′) are —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is aryl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isaryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² isaryl, R³ is aryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is heteroaryl, R³ is aryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with cycloalkyl, R³ isaryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² isalkyl substituted with heterocycloalkyl, R³ is aryl, and R⁴ and R^(4′)are —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted witharyl, R³ is aryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with heteroaryl, R³ is aryl, and R⁴ andR^(4′) are —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is heteroaryl, and R⁴and R^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³is heteroaryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is aryl, R³ is heteroaryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is heteroaryl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith cycloalkyl, R³ is heteroaryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heterocycloalkyl,R³ is heteroaryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is heteroaryl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is heteroaryl, and R⁴ and R^(4′) are —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith cycloalkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with cycloalkyl, and R⁴and R^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ isalkyl substituted with cycloalkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted withcycloalkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with cycloalkyl, R³ is alkyl substituted withcycloalkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heterocycloalkyl, R³ is alkyl substitutedwith cycloalkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is alkyl substituted withcycloalkyl, and R⁴ and R^(4′) are —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith aryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵, R²is cycloalkyl, R³ is alkyl substituted with aryl, and R⁴ and R^(4′) are—H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ is alkyl substitutedwith aryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵, R²is heteroaryl, R³ is alkyl substituted with aryl, and R⁴ and R^(4′) are—H. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with aryl, and R⁴ and R^(4′) are —H.In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, R³ is alkyl substituted with aryl, and R⁴ and R^(4′)are —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted witharyl, R³ is alkyl substituted with aryl, and R⁴ and R^(4′) are —H. Insome embodiments, R¹ is —OR⁵, R² is alkyl substituted with heteroaryl,R³ is alkyl substituted with aryl, and R⁴ and R^(4′) are —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith heteroaryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with heteroaryl, and R⁴and R^(4′) are —H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ isalkyl substituted with heteroaryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted withheteroaryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with cycloalkyl, R³ is alkyl substituted withheteroaryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heterocycloalkyl, R³ is alkyl substitutedwith heteroaryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is alkyl substituted withheteroaryl, and R⁴ and R^(4′) are —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isalkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R²is aryl, R³ is alkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl, R⁴ is —H and R^(4′) is —OH.In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withcycloalkyl, R³ is alkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heterocycloalkyl,R³ is alkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is alkyl, R⁴ is —H and R^(4′) is —OH.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is cycloalkyl, R⁴ is —Hand R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³is cycloalkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—OR⁵, R² is aryl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is cycloalkyl, R⁴ is —Hand R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is—OH. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ iscycloalkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is cycloalkyl, R⁴ is —H andR^(4′) is —OH.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is aryl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isaryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² isaryl, R³ is aryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—OR⁵, R² is heteroaryl, R³ is aryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with cycloalkyl, R³ isaryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² isalkyl substituted with heterocycloalkyl, R³ is aryl, R⁴ is —H and R^(4′)is —OH. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted witharyl, R³ is aryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with heteroaryl, R³ is aryl, R⁴ is —H andR^(4′) is —OH.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is heteroaryl, R⁴ is —Hand R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³is heteroaryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—OR⁵, R² is aryl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is heteroaryl, R⁴ is —Hand R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is—OH. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ isheteroaryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is heteroaryl, R⁴ is —H andR^(4′) is —OH.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is—H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ isalkyl substituted with cycloalkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with cycloalkyl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heterocycloalkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —OH.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith aryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵,R² is cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is —H and R^(4′)is —OH. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ is alkylsubstituted with aryl, R⁴ is —H and R^(4′) is —OH. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is—H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is —Hand R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with heterocycloalkyl, R³ is alkyl substituted with aryl, R⁴is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —H and R^(4′)is —OH.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is—H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ isalkyl substituted with heteroaryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with cycloalkyl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heterocycloalkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —OH.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isalkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R²is aryl, R³ is alkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl, R⁴ is —OH and R^(4′) is —H.In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withcycloalkyl, R³ is alkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heterocycloalkyl,R³ is alkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is alkyl, R⁴ is —OH and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is cycloalkyl, R⁴ is—OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl,R³ is cycloalkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is aryl, R³ is cycloalkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is cycloalkyl, R⁴ is —OHand R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is cycloalkyl, R⁴ is —OH and R^(4′) is—H. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ iscycloalkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is cycloalkyl, R⁴ is —OH andR^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is aryl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isaryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² isaryl, R³ is aryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is heteroaryl, R³ is aryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with cycloalkyl, R³ isaryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² isalkyl substituted with heterocycloalkyl, R³ is aryl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith aryl, R³ is aryl, R⁴ is —OH and R^(4′) is —H. In some embodiments,R¹ is —OR⁵, R² is alkyl substituted with heteroaryl, R³ is aryl, R⁴ is—OH and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is heteroaryl, R⁴ is—OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl,R³ is heteroaryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is aryl, R³ is heteroaryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is heteroaryl, R⁴ is —OHand R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is heteroaryl, R⁴ is —OH and R^(4′) is—H. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ isheteroaryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is heteroaryl, R⁴ is —OH andR^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is—OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ isalkyl substituted with cycloalkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with cycloalkyl, R³ is alkyl substituted withcycloalkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heterocycloalkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —OH and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith aryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ is alkylsubstituted with aryl, R⁴ is —OH and R^(4′) is —H. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is—OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is—OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with heterocycloalkyl, R³ is alkyl substituted with aryl, R⁴is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —OH and R^(4′)is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is—OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ isalkyl substituted with heteroaryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted withheteroaryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with cycloalkyl, R³ is alkyl substituted withheteroaryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heterocycloalkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is alkyl substituted withheteroaryl, R⁴ is —OH and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isalkyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R²is aryl, R³ is alkyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl, R⁴ is —H and R^(4′) is —NH₂.In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withcycloalkyl, R³ is alkyl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heterocycloalkyl,R³ is alkyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl, R⁴ is —H andR^(4′) is —NH₂.

In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheteroaryl, R³ is alkyl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —OR⁵, R² is alkyl, R³ is cycloalkyl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ iscycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—OR⁵, R² is aryl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is cycloalkyl, R⁴ is —Hand R^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is—NH₂. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ iscycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with heteroaryl, R³ is cycloalkyl, R⁴ is—H and R^(4′) is —NH₂.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is aryl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isaryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R²is aryl, R³ is aryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is aryl, R⁴ is —H and R^(4′) is —NH₂.In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withcycloalkyl, R³ is aryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heterocycloalkyl,R³ is aryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is aryl, R⁴ is —H and R^(4′)is —NH₂. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheteroaryl, R³ is aryl, R⁴ is —H and R^(4′) is —NH₂.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is heteroaryl, R⁴ is —Hand R^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl,R³ is heteroaryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹is —OR⁵, R² is aryl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —NH₂. Insome embodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is heteroaryl, R⁴ is—H and R^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is—NH₂. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ isheteroaryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with heteroaryl, R³ is heteroaryl, R⁴ is—H and R^(4′) is —NH₂.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is—H and R^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is aryl, R³is alkyl substituted with cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. Insome embodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with cycloalkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with heterocycloalkyl, R³ is alkylsubstituted with cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ is alkylsubstituted with cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heteroaryl, R³ isalkyl substituted with cycloalkyl, R⁴ is —H and R^(4′) is —NH₂.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith aryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵,R² is cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is —H and R^(4′)is —NH₂. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ is alkylsubstituted with aryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is—H and R^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is —Hand R^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with heterocycloalkyl, R³ is alkyl substituted with aryl, R⁴is —H and R^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —H and R^(4′)is —NH₂.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is—H and R^(4′) is —NH₂. In some embodiments, R¹ is —OR⁵, R² is aryl, R³is alkyl substituted with heteroaryl, R⁴ is —H and R^(4′) is —NH₂. Insome embodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with cycloalkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with heterocycloalkyl, R³ is alkylsubstituted with heteroaryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ is alkylsubstituted with heteroaryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heteroaryl, R³ isalkyl substituted with heteroaryl, R⁴ is —H and R^(4′) is —NH₂.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl, R⁴ is —NH₂and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³is alkyl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is aryl, R³ is alkyl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith cycloalkyl, R³ is alkyl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heterocycloalkyl,R³ is alkyl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is alkyl, R⁴ is —NH₂ and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is cycloalkyl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² iscycloalkyl, R³ is cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is aryl, R³ is cycloalkyl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is heteroaryl, R³ iscycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with cycloalkyl, R³ is cycloalkyl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with heterocycloalkyl, R³ is cycloalkyl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith aryl, R³ is cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heteroaryl, R³ iscycloalkyl, R⁴ is —NH₂ and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is aryl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isaryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R²is aryl, R³ is aryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is aryl, R⁴ is —NH₂ and R^(4′) is —H.In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withcycloalkyl, R³ is aryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heterocycloalkyl,R³ is aryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is aryl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is aryl, R⁴ is —NH₂ and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is heteroaryl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² iscycloalkyl, R³ is heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is aryl, R³ is heteroaryl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is heteroaryl, R³ isheteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with cycloalkyl, R³ is heteroaryl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with heterocycloalkyl, R³ is heteroaryl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith aryl, R³ is heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heteroaryl, R³ isheteroaryl, R⁴ is —NH₂ and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³is alkyl substituted with cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. Insome embodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with cycloalkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with heterocycloalkyl, R³ is alkylsubstituted with cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ is alkylsubstituted with cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heteroaryl, R³ isalkyl substituted with cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith aryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ is alkylsubstituted with aryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with heterocycloalkyl, R³ is alkyl substituted with aryl, R⁴is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —NH₂ andR^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³is alkyl substituted with heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. Insome embodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with cycloalkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with heterocycloalkyl, R³ is alkylsubstituted with heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ is alkylsubstituted with heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heteroaryl, R³ isalkyl substituted with heteroaryl, R⁴ is —NH₂ and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isalkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R²is aryl, R³ is alkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl, R⁴ is —H and R^(4′) is —CN.In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withcycloalkyl, R³ is alkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heterocycloalkyl,R³ is alkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is alkyl, R⁴ is —H and R^(4′) is —CN.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is cycloalkyl, R⁴ is —Hand R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³is cycloalkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—OR⁵, R² is aryl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is cycloalkyl, R⁴ is —Hand R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is—CN. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ iscycloalkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is cycloalkyl, R⁴ is —H andR^(4′) is —CN.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is aryl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isaryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² isaryl, R³ is aryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—OR⁵, R² is heteroaryl, R³ is aryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with cycloalkyl, R³ isaryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² isalkyl substituted with heterocycloalkyl, R³ is aryl, R⁴ is —H and R^(4′)is —CN. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted witharyl, R³ is aryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with heteroaryl, R³ is aryl, R⁴ is —H andR^(4′) is —CN.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is heteroaryl, R⁴ is —Hand R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³is heteroaryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—OR⁵, R² is aryl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is heteroaryl, R⁴ is —Hand R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is—CN. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ isheteroaryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is heteroaryl, R⁴ is —H andR^(4′) is —CN.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is—H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ isalkyl substituted with cycloalkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with cycloalkyl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heterocycloalkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —CN.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith aryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵,R² is cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is —H and R^(4′)is —CN. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ is alkylsubstituted with aryl, R⁴ is —H and R^(4′) is —CN. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is—H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is —Hand R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with heterocycloalkyl, R³ is alkyl substituted with aryl, R⁴is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —H and R^(4′)is —CN.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is—H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ isalkyl substituted with heteroaryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with cycloalkyl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heterocycloalkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —CN.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isalkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R²is aryl, R³ is alkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl, R⁴ is —CN and R^(4′) is —H.In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withcycloalkyl, R³ is alkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with heterocycloalkyl,R³ is alkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is alkyl, R⁴ is —CN and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is cycloalkyl, R⁴ is—CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl,R³ is cycloalkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is aryl, R³ is cycloalkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is cycloalkyl, R⁴ is —CNand R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is cycloalkyl, R⁴ is —CN and R^(4′) is—H. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ iscycloalkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is cycloalkyl, R⁴ is —CN andR^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is aryl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl, R³ isaryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² isaryl, R³ is aryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is heteroaryl, R³ is aryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with cycloalkyl, R³ isaryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² isalkyl substituted with heterocycloalkyl, R³ is aryl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith aryl, R³ is aryl, R⁴ is —CN and R^(4′) is —H. In some embodiments,R¹ is —OR⁵, R² is alkyl substituted with heteroaryl, R³ is aryl, R⁴ is—CN and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is heteroaryl, R⁴ is—CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is cycloalkyl,R³ is heteroaryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is aryl, R³ is heteroaryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is heteroaryl, R⁴ is —CNand R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is heteroaryl, R⁴ is —CN and R^(4′) is—H. In some embodiments, R¹ is —OR⁵, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is alkyl substituted with aryl, R³ isheteroaryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is heteroaryl, R⁴ is —CN andR^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is—CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ isalkyl substituted with cycloalkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with cycloalkyl, R³ is alkyl substituted withcycloalkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heterocycloalkyl, R³ is alkyl substitutedwith cycloalkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —CN and R^(4′) is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith aryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ is alkylsubstituted with aryl, R⁴ is —CN and R^(4′) is —H. In some embodiments,R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is—CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with cycloalkyl, R³ is alkyl substituted with aryl, R⁴ is—CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with heterocycloalkyl, R³ is alkyl substituted with aryl, R⁴is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is alkyl substitutedwith heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —CN and R^(4′)is —H.

In some embodiments, R¹ is —OR⁵, R² is alkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is cycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is—CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵, R² is aryl, R³ isalkyl substituted with heteroaryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —OR⁵, R² is heteroaryl, R³ is alkyl substituted withheteroaryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with cycloalkyl, R³ is alkyl substituted withheteroaryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heterocycloalkyl, R³ is alkyl substitutedwith heteroaryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—OR⁵, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is —OR⁵,R² is alkyl substituted with heteroaryl, R³ is alkyl substituted withheteroaryl, R⁴ is —CN and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl and R² is alkyl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl and R² iscycloalkyl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl and R² is aryl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl and R² isheteroaryl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl and R² is alkyl substituted with cycloalkyl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl and R² is alkyl substituted with heterocycloalkyl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl and R² is alkyl substituted with aryl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl and R² isalkyl substituted with heteroaryl.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, and R³ is alkyl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² iscycloalkyl, and R³ is alkyl. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is aryl, and R³ is alkyl. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, and R³ is alkyl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with cycloalkyl, and R³ is alkyl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heterocycloalkyl, and R³ is alkyl. In some embodiments,R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, and R³ is alkyl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, and R³ is alkyl.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, and R³ is cycloalkyl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² iscycloalkyl, and R³ is cycloalkyl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,and R³ is cycloalkyl. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is heteroaryl, and R³ iscycloalkyl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with cycloalkyl, and R³ iscycloalkyl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, andR³ is cycloalkyl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with aryl, and R³ iscycloalkyl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, and R³ iscycloalkyl.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, and R³ is aryl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² iscycloalkyl, and R³ is aryl. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is aryl, and R³ is aryl. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, and R³ is aryl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with cycloalkyl, and R³ is aryl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heterocycloalkyl, and R³ is aryl. In some embodiments,R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, and R³ is aryl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, and R³ is aryl.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, and R³ is heteroaryl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² iscycloalkyl, and R³ is heteroaryl. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,and R³ is heteroaryl. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is heteroaryl, and R³ isheteroaryl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with cycloalkyl, and R³ isheteroaryl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, andR³ is heteroaryl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with aryl, and R³ isheteroaryl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, and R³ isheteroaryl.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, and R³ is alkyl substituted with cycloalkyl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, and R³ is alkyl substituted with cycloalkyl. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, and R³ is alkyl substituted with cycloalkyl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, and R³ is alkyl substituted with cycloalkyl. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, and R³ is alkylsubstituted with cycloalkyl. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, and R³ is alkyl substituted with cycloalkyl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, and R³ is alkyl substitutedwith cycloalkyl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, and R³ isalkyl substituted with cycloalkyl.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, and R³ is alkyl substituted with aryl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, and R³ is alkyl substituted with aryl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, and R³ is alkyl substituted with aryl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, and R³ is alkyl substituted with aryl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, and R³ is alkylsubstituted with aryl. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, and R³ is alkyl substituted with aryl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, and R³ is alkyl substitutedwith aryl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, and R³ isalkyl substituted with aryl.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, and R³ is alkyl substituted with heteroaryl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, and R³ is alkyl substituted with heteroaryl. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, and R³ is alkyl substituted with heteroaryl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, and R³ is alkyl substituted with heteroaryl. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, and R³ is alkylsubstituted with heteroaryl. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, and R³ is alkyl substituted with heteroaryl. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, and R³ is alkyl substitutedwith heteroaryl. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, and R³ isalkyl substituted with heteroaryl.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is alkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is alkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is alkyl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is alkyl, and R⁴ andR^(4′) are —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is cycloalkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is cycloalkyl, and R⁴ and R^(4′) are —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is cycloalkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is cycloalkyl, and R⁴ and R^(4′) are —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is cycloalkyl, and R⁴and R^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is cycloalkyl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ iscycloalkyl, and R⁴ and R^(4′) are —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is aryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is aryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is aryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is aryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is aryl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is aryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is aryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is aryl, and R⁴ andR^(4′) are —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is heteroaryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is heteroaryl, and R⁴ and R^(4′) are —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is heteroaryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is heteroaryl, and R⁴ and R^(4′) are —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is heteroaryl, and R⁴and R^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is heteroaryl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isheteroaryl, and R⁴ and R^(4′) are —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with cycloalkyl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withcycloalkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with cycloalkyl, and R⁴ and R^(4′) are —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with cycloalkyl, and R⁴and R^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with cycloalkyl, and R⁴ and R^(4′)are —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with cycloalkyl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with cycloalkyl,and R⁴ and R^(4′) are —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with aryl, and R⁴ and R^(4′)are —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted witharyl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is aryl, R³ is alkylsubstituted with aryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² isheteroaryl, R³ is alkyl substituted with aryl, and R⁴ and R^(4′) are —H.In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is alkyl substitutedwith aryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heterocycloalkyl, R³ is alkyl substituted with aryl,and R⁴ and R^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted witharyl, R³ is alkyl substituted with aryl, and R⁴ and R^(4′) are —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is alkyl substitutedwith aryl, and R⁴ and R^(4′) are —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with heteroaryl, and R⁴ andR^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withheteroaryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with heteroaryl, and R⁴ and R^(4′) are —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with heteroaryl, and R⁴and R^(4′) are —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with heteroaryl, and R⁴ and R^(4′)are —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with heteroaryl, and R⁴ and R^(4′) are —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, and R⁴ and R^(4′) are —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with heteroaryl,and R⁴ and R^(4′) are —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is alkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is alkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is alkyl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is alkyl, R⁴ is —H andR^(4′) is —OH.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —OH. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —OH.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is cycloalkyl, R⁴ is—H and R^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is cycloalkyl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ iscycloalkyl, R⁴ is —H and R^(4′) is —OH.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is aryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is aryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is aryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is aryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is aryl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is aryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is aryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is aryl, R⁴ is —H andR^(4′) is —OH.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —OH. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —OH.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is heteroaryl, R⁴ is—H and R^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is heteroaryl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isheteroaryl, R⁴ is —H and R^(4′) is —OH.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with cycloalkyl, R⁴ is —H and R^(4′) is —OH. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴ is—H and R^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —H and R^(4′)is —OH. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with cycloalkyl, R⁴ is —H and R^(4′) is —OH. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴is —H and R^(4′) is —OH.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted witharyl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with aryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with cycloalkyl, R³ isalkyl substituted with aryl, R⁴ is —H and R^(4′) is —OH. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heterocycloalkyl, R³ is alkylsubstituted with aryl, R⁴ is —H and R^(4′) is —OH. In some embodiments,R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isalkyl substituted with aryl, R⁴ is —H and R^(4′) is —OH.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —H andR^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with heteroaryl, R⁴ is —H and R^(4′) is —OH. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴ is—H and R^(4′) is —OH. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —H and R^(4′)is —OH. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with heteroaryl, R⁴ is —H and R^(4′) is —OH. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —OH. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴is —H and R^(4′) is —OH.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is alkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is alkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is alkyl, R⁴ is —OHand R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is alkyl, R⁴ is —OHand R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is cycloalkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is cycloalkyl, R⁴ is —OH and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is cycloalkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is cycloalkyl, R⁴ is —OH and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is cycloalkyl, R⁴ is—OH and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is cycloalkyl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ iscycloalkyl, R⁴ is —OH and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is aryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is aryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is aryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is aryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is aryl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is aryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is aryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is aryl, R⁴ is —OH andR^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is heteroaryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is heteroaryl, R⁴ is —OH and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is heteroaryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is heteroaryl, R⁴ is —OH and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is heteroaryl, R⁴ is—OH and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is heteroaryl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isheteroaryl, R⁴ is —OH and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —OHand R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withcycloalkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with cycloalkyl, R⁴ is —OH and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴ is—OH and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with cycloalkyl, R⁴ is —OH and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴is —OH and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with aryl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted witharyl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with aryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with cycloalkyl, R³ isalkyl substituted with aryl, R⁴ is —OH and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heterocycloalkyl, R³ is alkylsubstituted with aryl, R⁴ is —OH and R^(4′) is —H. In some embodiments,R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isalkyl substituted with aryl, R⁴ is —OH and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —OHand R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withheteroaryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with heteroaryl, R⁴ is —OH and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴ is—OH and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —OH andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with heteroaryl, R⁴ is —OH and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, R⁴ is —OH and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴is —OH and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is alkyl, R⁴ is —H and R^(4′) is —NH₂. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is alkyl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl, R⁴ is —H and R^(4′) is —NH₂. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is alkyl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl, R⁴ is —H and R^(4′) is —NH₂.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is alkyl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′)is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is cycloalkyl, R⁴ is —H andR^(4′) is —NH₂.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —NH₂.In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is cycloalkyl, R⁴ is—H and R^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is cycloalkyl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ iscycloalkyl, R⁴ is —H and R^(4′) is —NH₂.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is aryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is aryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is aryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is aryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is aryl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is aryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is aryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is aryl, R⁴ is —H andR^(4′) is —NH₂.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —NH₂. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —NH₂.In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —NH₂.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is heteroaryl, R⁴ is—H and R^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is heteroaryl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isheteroaryl, R⁴ is —H and R^(4′) is —NH₂.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴ is—H and R^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —H and R^(4′)is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with cycloalkyl, R⁴ is —H and R^(4′) is —NH₂. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴is —H and R^(4′) is —NH₂.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted witharyl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with aryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with cycloalkyl, R³ isalkyl substituted with aryl, R⁴ is —H and R^(4′) is —NH₂. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heterocycloalkyl, R³ is alkylsubstituted with aryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments,R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isalkyl substituted with aryl, R⁴ is —H and R^(4′) is —NH₂.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —H andR^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with heteroaryl, R⁴ is —H and R^(4′) is —NH₂. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴ is—H and R^(4′) is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —H and R^(4′)is —NH₂. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with heteroaryl, R⁴ is —H and R^(4′) is —NH₂. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —NH₂. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴is —H and R^(4′) is —NH₂.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is alkyl, R⁴ is —NH₂ and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is alkyl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl, R⁴ is —NH₂ and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is alkyl, R⁴ is —NH₂and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is alkyl, R⁴ is —NH₂and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H.In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H.In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is cycloalkyl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is cycloalkyl, R⁴ is —NH₂and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ iscycloalkyl, R⁴ is —NH₂ and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is aryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is aryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is aryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is aryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is aryl, R⁴ is —NH₂and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is aryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is aryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is aryl, R⁴ is —NH₂and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is heteroaryl, R⁴ is —NH₂ and R^(4′) is —H.In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is heteroaryl, R⁴ is —NH₂ and R^(4′) is —H.In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is heteroaryl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is heteroaryl, R⁴ is —NH₂and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isheteroaryl, R⁴ is —NH₂ and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —NH₂and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withcycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with cycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴is —NH₂ and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with aryl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted witharyl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with aryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —NH₂and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with cycloalkyl, R³ isalkyl substituted with aryl, R⁴ is —NH₂ and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heterocycloalkyl, R³ is alkylsubstituted with aryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments,R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isalkyl substituted with aryl, R⁴ is —NH₂ and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —NH₂and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withheteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴ is—NH₂ and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —NH₂ andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with heteroaryl, R⁴ is —NH₂ and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, R⁴ is —NH₂ and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴is —NH₂ and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is alkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is alkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is alkyl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is alkyl, R⁴ is —H andR^(4′) is —CN.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —CN. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —CN. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is cycloalkyl, R⁴ is—H and R^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is cycloalkyl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ iscycloalkyl, R⁴ is —H and R^(4′) is —CN.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is aryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is aryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is aryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is aryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is aryl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is aryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is aryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is aryl, R⁴ is —H andR^(4′) is —CN.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —CN. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —CN. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is heteroaryl, R⁴ is—H and R^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is heteroaryl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isheteroaryl, R⁴ is —H and R^(4′) is —CN.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with cycloalkyl, R⁴ is —H and R^(4′) is —CN. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴ is—H and R^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —H and R^(4′)is —CN. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with cycloalkyl, R⁴ is —H and R^(4′) is —CN. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴is —H and R^(4′) is —CN.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted witharyl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with aryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with cycloalkyl, R³ isalkyl substituted with aryl, R⁴ is —H and R^(4′) is —CN. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heterocycloalkyl, R³ is alkylsubstituted with aryl, R⁴ is —H and R^(4′) is —CN. In some embodiments,R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isalkyl substituted with aryl, R⁴ is —H and R^(4′) is —CN.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —H andR^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with heteroaryl, R⁴ is —H and R^(4′) is —CN. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴ is—H and R^(4′) is —CN. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —H and R^(4′)is —CN. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with heteroaryl, R⁴ is —H and R^(4′) is —CN. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, R⁴ is —H and R^(4′) is —CN. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴is —H and R^(4′) is —CN.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is alkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is alkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is alkyl, R⁴ is —CNand R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is alkyl, R⁴ is —CNand R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is cycloalkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is cycloalkyl, R⁴ is —CN and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is cycloalkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is cycloalkyl, R⁴ is —CN and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is cycloalkyl, R⁴ is—CN and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is cycloalkyl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is cycloalkyl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ iscycloalkyl, R⁴ is —CN and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is aryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is aryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is aryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is aryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is aryl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is aryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is aryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heteroaryl, R³ is aryl, R⁴ is —CN andR^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is heteroaryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is cycloalkyl, R³ is heteroaryl, R⁴ is —CN and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is aryl, R³ is heteroaryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is heteroaryl, R⁴ is —CN and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with cycloalkyl, R³ is heteroaryl, R⁴ is—CN and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withheterocycloalkyl, R³ is heteroaryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is heteroaryl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isheteroaryl, R⁴ is —CN and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —CNand R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withcycloalkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with cycloalkyl, R⁴ is —CN and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴ is—CN and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with cycloalkyl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with cycloalkyl, R⁴ is —CN and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withcycloalkyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with cycloalkyl, R⁴is —CN and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with aryl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted witharyl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with aryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with aryl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with cycloalkyl, R³ isalkyl substituted with aryl, R⁴ is —CN and R^(4′) is —H. In someembodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with heterocycloalkyl, R³ is alkylsubstituted with aryl, R⁴ is —CN and R^(4′) is —H. In some embodiments,R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with aryl, R³ is alkyl substituted with aryl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heteroaryl, R³ isalkyl substituted with aryl, R⁴ is —CN and R^(4′) is —H.

In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —CNand R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is cycloalkyl, R³ is alkyl substituted withheteroaryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is aryl,R³ is alkyl substituted with heteroaryl, R⁴ is —CN and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴ is—CN and R^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocycloalkyl, heteroaryl, or aryl, R² is alkyl substituted withcycloalkyl, R³ is alkyl substituted with heteroaryl, R⁴ is —CN andR^(4′) is —H. In some embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl,heteroaryl, or aryl, R² is alkyl substituted with heterocycloalkyl, R³is alkyl substituted with heteroaryl, R⁴ is —CN and R^(4′) is —H. Insome embodiments, R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, oraryl, R² is alkyl substituted with aryl, R³ is alkyl substituted withheteroaryl, R⁴ is —CN and R^(4′) is —H. In some embodiments, R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocycloalkyl, heteroaryl, or aryl, R² is alkylsubstituted with heteroaryl, R³ is alkyl substituted with heteroaryl, R⁴is —CN and R^(4′) is —H.

Compounds of the present disclosure can be compounds wherein R⁶ is aryl,optionally substituted with one or two R¹⁰, wherein R¹⁰ isindependently, at each occurrence, halogen or —OC₁-C₆alkyl, wherein—OC₁-C₆alkyl is optionally substituted with halogen.

Compounds of the present disclosure can comprise aryl, wherein aryl canbe ring systems having a total of five to fourteen ring members, whereinat least one ring in the system is aromatic and wherein each ring in thesystem contains 3 to 7 ring members. For example, aryl can include, butare is not limited to, phenyl.

Compounds of the present disclosure can comprise heteroaryl, whereinheteroaryl is a group having 5 to 10 ring atoms, preferably 5, 6, or 9ring atoms; having 6, 10, or 14π electrons shared in a cyclic array;and/or having, in addition to carbon atoms, from one to five heteroatomswherein the term “heteroatom” refers to nitrogen, oxygen, or sulfur, andincludes any oxidized form of nitrogen or sulfur, and any quaternizedform of a basic nitrogen. For example, heteroaryl can include, but areis not limited to, pyridine, indole, benzapyrazole, benzoxale,furopyridine, or isoquinoline.

Compounds of the present disclosure can comprise heterocycl, whereinheterocyclyl is a stable 5- to 7-membered monocyclic or 7-10-memberedbicyclic heterocyclic moiety that is either saturated or partiallyunsaturated, and having, in addition to carbon atoms, one or more,preferably one to four, heteroatoms, as defined above. For example,heterocyclyl can include, but are is not limited to, dihydrofuran,dihydrofuropyrine or dihydroisofuran.

Method of Synthesizing the Compounds

The compounds of the present disclosure may be made by a variety ofmethods, including standard chemistry. Suitable synthetic routes aredepicted in the examples given below.

The compounds of the present disclosure, i.e., compounds of Formula (I),or a pharmaceutically acceptable salt, enantiomer, hydrate, solvate,prodrug, isomer, or tautomer thereof, may be prepared by organicsynthesis such as those as set forth in part by the following syntheticschemes. In the schemes described below, it is well understood thatprotecting groups for sensitive or reactive groups are employed wherenecessary in accordance with general principles or chemistry. Protectinggroups are manipulated according to standard methods of organicsynthesis (T. W. Greene and P. G. M. Wuts, “Protective Groups in OrganicSynthesis”, Third edition, Wiley, New York 1999). These groups areremoved at a convenient stage of the compound synthesis using methodsthat are readily apparent to those skilled in the art. The selectionprocesses, as well as the reaction conditions and order of theirexecution, shall be consistent with the preparation of compounds ofFormula (I).

Those skilled in the art will recognize if a stereocenter exists in thecompounds of Formula (I). Accordingly, unless otherwise indicated, thepresent disclosure includes both possible stereoisomers (unlessspecified in the synthesis) and includes not only racemic compounds butthe individual enantiomers and/or diastereomers as well. When a compoundis desired as a single enantiomer or diastereomer, it may be obtained bystereospecific synthesis or by resolution of the final product or anyconvenient intermediate. Resolution of the final product, anintermediate, or a starting material may be affected by any suitablemethod known in the art. See, for example, “Stereochemistry of OrganicCompounds” by E. L. Eliel, S. H. Wilen, and L. N. Mander(Wiley-lnterscience, 1994).

The compounds described herein may be made from commercially availablestarting materials or synthesized using known organic, inorganic, and/orenzymatic processes.

Methods of Using the Disclosed Compounds

One aspect of the present disclosure relates to a compound of Formula(I) for use in medicine. Another aspect of the present disclosurerelates to a method of modulating one or more of CBP/p300-familybromodomains, comprising administering to a patient in need thereof atherapeutically effective amount of a compound of Formula (I). Anotheraspect of the present disclosure relates to a method of inhibiting oneor more of CBP/p300-family bromodomains, comprising administering to apatient in need thereof a therapeutically effective amount of a compoundof Formula (I). In another aspect, the present disclosure relates to amethod of inhibiting one or more of CBP/p300-family bromodomains,comprising administering to a patient in need thereof a therapeuticallyeffective amount of a pharmaceutical composition comprising a compoundof Formula (I).

In another aspect, the ratio of inhibition of CBP (IC₅₀ (μM gmean)) ascompared to the inhibition of BRD4 (IC₅₀ (μM gmean)) is determined. Insome embodiments, the inhibition of CBP (IC₅₀ (μM gmean)) is determinedas outlined in Example 963. In some embodiments, the inhibition of BRD4(IC₅₀ (μM gmean)) is determined as outlined in Example 963. It will beappreciated that a positive ratio of inhibition for CBP vs. BRD4indicates that a compound selectively inhibits CBP over BRD4. In someembodiments, a compound is characterized in that the ratio of CBP IC₅₀to BRD4 IC₅₀ is 10:1. In some embodiments, a compound is characterizedin that the ratio of CBP IC₅₀ to BRD4 IC₅₀ is 20:1. In some embodiments,a compound is characterized in that the ratio of CBP IC₅₀ to BRD4 IC₅₀is 50:1. In some embodiments, a compound is characterized in that theratio of CBP IC₅₀ to BRD4 IC₅₀ is 100:1. In some embodiments, a compoundis characterized in that the ratio of CBP IC₅₀ to BRD4 IC₅₀ is 250:1. Insome embodiments, a compound is characterized in that the ratio of CBPIC₅₀ to BRD4 IC₅₀ is 500:1. In some embodiments, a compound ischaracterized in that the ratio of CBP IC₅₀ to BRD4 IC₅₀ is 750:1. Insome embodiments, the ratio of CBP IC₅₀ to BRD4 IC₅₀ is 1,000:1. In someembodiments, a compound is characterized in that the ratio of CBP IC₅₀to BRD4 IC₅₀ is 2,500:1. In some embodiments, a compound ischaracterized in that the ratio of CBP IC₅₀ to BRD4 IC₅₀ is 5,000:1. Insome embodiments, a compound is characterized in that the ratio of CBPIC₅₀ to BRD4 IC₅₀ is 10,000:1. In some embodiments, a compound ischaracterized in that is has a BRD4 IC₅₀ of greater than 0.01 μM. Insome embodiments, a compound is characterized in that is has a BRD4 IC₅₀of greater than 0.1 μM. In some embodiments, a compound is characterizedin that is has a BRD4 IC₅₀ of greater than 1 μM.

Another aspect of the present disclosure relates to a method oftreating, preventing, inhibiting, or eliminating a disease or disorderin a patient associated with the inhibition of one or more ofCBP/p300-family bromodomains, the method comprising administering atherapeutically effective amount of a compound of Formula (I). In oneembodiment, the disease or disorder is selected from the groupconsisting of cancer. In some embodiments, the cancer is a solid tumor.In some embodiments, the cancer is cancer of the prostate includingcastration-resistant prostate cancer, and breast cancer.

The present disclosure also relates to the use of an inhibitor ofCBP/p300 family bromodomains for the preparation of a medicament used inthe treatment, prevention, inhibition or elimination of a disease ordisorder mediated by CBP/p300 family bromodomains, wherein themedicament comprises a compound of Formula (I). In another aspect, thepresent disclosure relates to a method for the manufacture of amedicament for treating, preventing, inhibiting, or eliminating adisease or disorder mediated by CBP/p300 family bromodomains, whereinthe medicament comprises a compound of Formula (I). Another aspect ofthe present disclosure relates to a pharmaceutical composition for usein a method for treating a disease or disorder mediated by CBP/p300family bromodomains, wherein the pharmaceutical composition comprises acompound of Formula (I). In yet another aspect, the present disclosurerelates to a compound for use in a method for treating a disease ordisorder mediated by CBP/p300 family bromodomains, wherein the compoundcomprises a compound of Formula (I).

The present disclosure also relates to the use of an inhibitor ofCBP/p300 family bromodomains for the preparation of a medicament used inthe treatment, prevention, inhibition or elimination of tumors, whereinthe medicament comprises a compound of Formula (I). The presentdisclosure further relates to the use of an inhibitor of CBP/p300 familybromodomains for the preparation of a medicament used in the treatment,prevention, inhibition or elimination of cancer, wherein the medicamentcomprises a compound of Formula (I).

Another embodiment of the present disclosure relates to a compound ofFormula (I), or a pharmaceutically acceptable salt, enantiomer, hydrate,solvate, prodrug, isomer, or tautomer thereof, or a pharmaceuticalcomposition comprising a compound of the present disclosure, or apharmaceutically acceptable salt, enantiomer, hydrate, solvate, prodrug,isomer, or tautomer thereof, and a pharmaceutically acceptable carrierwhich provides, upon administration to a human, a decrease in tumorburden and/or metastases.

The disclosure is directed to compounds as described herein andpharmaceutically acceptable salts, enantiomers, hydrates, solvates,prodrugs, isomers, or tautomers thereof, and pharmaceutical compositionscomprising one or more compounds as described herein, orpharmaceutically acceptable salts, enantiomers, hydrates, solvates,prodrugs, isomers, or tautomers thereof. The disclosure is directed tocompounds as described herein and pharmaceutically acceptable saltsthereof. The disclosure also includes pharmaceutical compositionscomprising one or more compounds as described herein, or apharmaceutically acceptable salt thereof, and a pharmaceuticallyacceptable excipient. In some embodiments, pharmaceutical compositionsreported herein can be provided in a unit dosage form container (e.g.,in a vial or bag or the like). In some embodiments, pharmaceuticalcompositions reported herein can be provided in an oral dosage form. Insome embodiments, an oral dosage form of a compound of Formula (I) canbe a capsule. In some embodiments, an oral dosage form of a compound ofFormula (I) is a tablet. In some embodiments, an oral dosage formcomprises one or more fillers, disintigrants, lubricants, glidants,anti-adherents and/or anti-statics. In some embodiments, an oral dosageform is prepared via dry blending. In some embodiments, an oral dosageform is a tablet and is prepared via dry granulation.

The present disclosure also relates to a pharmaceutical compositioncomprising a compound of Formula (I) and a pharmaceutically acceptablecarrier. The pharmaceutical acceptable carrier may further include anexcipient, diluent, additive, or surfactant. The compounds orpharmaceutical compositions of the disclosure may be administered viaany mode of administration for therapeutic agents. These modes includesystemic or local administration such as oral administration. Dependingon the intended mode of administration, the disclosed compounds orcompositions can be in solid dosage form, such as, for example, tablets,or pills or the like, sometimes in unit dosages and consistent withconventional pharmaceutical practices. Likewise, they can also beadministered using forms well known to those skilled in thepharmaceutical arts.

In one embodiment, the present disclosure relates to a method ofpreparing a pharmaceutical composition of the present disclosure bymixing at least one pharmaceutically acceptable compound of the presentdisclosure, and, optionally, one or more pharmaceutically acceptablecarriers, additives, or excipients. Pharmaceutical compositionscomprising a CBP Inhibitor can be prepared according to conventionalmixing, granulating or coating methods, respectively, and the presentpharmaceutical compositions can contain from about 0.1% to about 99%,from about 5% to about 90%, or from about 1% to about 20% of thedisclosed compound by weight or volume. The dosage forms of the presentdisclosure, may contain a mixture of one or more compounds of thisdisclosure, and may include additional materials known to those skilledin the art as pharmaceutical excipients. Stabilizing additives may beincorporated into the delivery agent solution. With some drugs, thepresence of such additives promotes the stability and dispersibility ofthe agent in solution. The stabilizing additives may be employed at aconcentration ranging from about 0.1 and 5% (W/V), preferably about 0.5%(W/V). Suitable, but non-limiting, examples of stabilizing additivesinclude gum acacia, gelatin, methyl cellulose, polyethylene glycol,carboxylic acids and salts thereof, and polylysine. In one embodiment,the stabilizing additives are gum acacia, gelatin and methyl cellulose.

Examples of pharmaceutical excipients and additives include, but are notlimited to: acidifying agents (acetic acid, glacial acetic acid, citricacid, fumaric acid, hydrochloric acid, diluted hydrochloric acid, malicacid, nitric acid, phosphoric acid, diluted phosphoric acid, sulfuricacid, tartaric acid); Aerosol propellants (butane,dichlorodifluoro-methane, dichlorotetrafluoroethane, isobutane, propane,trichloromonofluoromethane); Air displacements (carbon dioxide,nitrogen); Alcohol denaturants (denatonium benzoate, methyl isobutylketone, sucrose octaacetate); Alkalizing agents (strong ammoniasolution, ammonium carbonate, diethanolamine, diisopropanolamine,potassium hydroxide, sodium bicarbonate, sodium borate, sodiumcarbonate, sodium hydroxide, trolamine); Anticaking agents (seeglidant); Antifoaming agents (dimethicone, simethicone); Antimicrobialpreservatives (benzalkonium chloride, benzalkonium chloride solution,benzelthonium chloride, benzoic acid, benzyl alcohol, butylparaben,cetylpyridinium chloride, chlorobutanol, chlorocresol, cresol,dehydroacetic acid, ethylparaben, methylparaben, methylparaben sodium,phenol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuricnitrate, potassium benzoate, potassium sorbate, propylparaben,propylparaben sodium, sodium benzoate, sodium dehydroacetate, sodiumpropionate, sorbic acid, thimerosal, thymol); Antioxidants (ascorbicacid, ascorbyl palmitate, butylated hydroxyanisole, butylatedhydroxytoluene, hypophosphorous acid, monothioglycerol, propyl gallatesodium formaldehyde sulfoxylate sodium metabisulfite, sodiumthiosulfate, sulfur dioxide, tocopherol, tocopherols excipient);Buffering agents (acetic acid, ammonium carbonate, ammonium phosphate,boric acid, citric acid, lactic acid, phosphoric acid, potassiumcitrate, potassium metaphosphate, potassium phosphate monobasic, sodiumacetate, sodium citrate, sodium lactate solution, dibasic sodiumphosphate, monobasic sodium phosphate); Capsule lubricants (see tabletand capsule lubricant); Chelating agents (edetate disodium,ethylenediaminetetraacetic acid and salts, edetic acid); Coating agents(sodium carboxymethylcellulose, cellulose acetate, cellulose acetatephthalate ethylcellulose, gelatin, pharmaceutical glaze, hydroxypropylcellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulosephthalate methacrylic acid copolymer, methylcellulose, polyethyleneglycol, polyvinyl acetate phthalate shellac, sucrose, titanium dioxide,carnauba wax, microcrystalline wax, zein); Colorants (caramel, red,yellow, black or blends, ferric oxide); Complexing agents(ethylenediaminetetraacetic acid and salts (EDTA), edetic acid, gentisicacid ethanolamide, oxyquinoline sulfate); Desiccants (calcium chloride,calcium sulfate, silicon dioxide); Emulsifying and/or solubilizingagents (acacia, cholesterol, diethanolamine (adjunct), glycerylmonostearate, lanolin alcohols, lecithin, mono- and di-glycerides,monoethanolamine (adjunct), oleic acid (adjunct), oleyl alcohol(stabilizer), poloxamer, polyoxyethylene 50 stearate, polyoxyl 35 casteroil, polyoxyl 40 hydrogenated castor oil, polyoxyl 10 oleyl ether,polyoxyl 20 cetostearyl ether, polyoxyl 40 stearate, polysorbate 20,polysorbate 40, polysorbate 60, polysorbate 80, propylene glycoldiacetate, propylene glycol monostearate, sodium lauryl sulfate, sodiumstearate, sorbitan monolaurate, sorbitan monooleate, sorbitanmonopalmitate, sorbitan monostearate, stearic acid, trolamine,emulsifying wax); Filtering aids (powdered cellulose, purified siliceousearth); Flavors and perfumes (anethole, benzaldehyde, ethyl vanillin,menthol, methyl salicylate monosodium glutamate, orange flower oil,peppermint, peppermint oil, peppermint spirit, rose oil, stronger rosewater, thymol, tolu balsam tincture, vanilla, vanilla tincture,vanillin); Glidants and/or anticaking agents (calcium silicate,magnesium silicate, colloidal silicon dioxide, talc); Humectants(glycerin, hexylene glycol, propylene glycol, sorbitol); Plasticizers(castor oil, diacetylated monoglycerides, diethyl phthalate glycerin,mono- and di-acetylated monoglycerides, polyethylene glycol, propyleneglycol, triacetin, triethyl citrate); Polymers (e.g., cellulose acetate,alkyl celluloses, hydroxyalkylcelluloses, acrylic polymers andcopolymers); Solvents (acetone, alcohol, diluted alcohol, amylenehydrate, benzyl benzoate, butyl alcohol, carbon tetrachloride,chloroform, corn oil, cottonseed oil, ethyl acetate, glycerin, hexyleneglycol, isopropyl alcohol, methyl alcohol, methylene chloride, methylisobutyl ketone, mineral oil, peanut oil, polyethylene glycol, propylenecarbonate, propylene glycol, sesame oil, water for injection, sterilewater for injection, sterile water for irrigation, purified water);Sorbents (powdered cellulose, charcoal, purified siliceous earth);Carbon dioxide sorbents (barium hydroxide lime, soda lime); Stiffeningagents (hydrogenated castor oil, cetostearyl alcohol, cetyl alcohol,cetyl esters wax, hard fat, paraffin, polyethylene excipient, stearylalcohol, emulsifying wax, white wax, yellow wax); Suspending and/orviscosity-increasing agents (acacia, agar, alginic acid, aluminummonostearate, bentonite, purified bentonite, magma bentonite, carbomer934p, carboxymethylcellulose calcium, carboxymethylcellulose sodium,carboxymethylcellulose sodium 12, carrageenan, microcrystalline andcarboxymethylcellulose sodium cellulose, dextrin, gelatin, guar gum,hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethylcellulose, magnesium aluminum silicate, methylcellulose, pectin,polyethylene oxide, polyvinyl alcohol, povidone, propylene glycolalginate, silicon dioxide, colloidal silicon dioxide, sodium alginate,tragacanth, xanthan gum); Sweetening agents (aspartame, dextrates,dextrose, excipient dextrose, fructose, mannitol, saccharin, calciumsaccharin, sodium saccharin, sorbitol, solution sorbitol, sucrose,compressible sugar, confectioner's sugar, syrup); Tablet binders(acacia, alginic acid, sodium carboxymethylcellulose, microcrystallinecellulose, dextrin, ethylcellulose, gelatin, liquid glucose, guar gum,hydroxypropyl methylcellulose, methylcellulose, polyethylene oxide,povidone, pregelatinized starch, syrup); Tablet and/or capsule diluents(calcium carbonate, dibasic calcium phosphate, tribasic calciumphosphate, calcium sulfate, microcrystalline cellulose, powderedcellulose, dextrates, dextrin, dextrose excipient, fructose, kaolin,lactose, mannitol, sorbitol, starch, pregelatinized starch, sucrose,compressible sugar, confectioner's sugar); Tablet disintegrants (alginicacid, microcrystalline cellulose, croscarmellose sodium, crospovidone,polacrilin potassium, sodium starch glycolate starch, pregelatinizedstarch); Tablet and/or capsule lubricants (calcium stearate, glycerylbehenate, magnesium stearate, light mineral oil, polyethylene glycol,sodium stearyl fumarate, stearic acid, purified stearic acid, talc,hydrogenated vegetable oil, zinc stearate); Tonicity agent (dextrose,glycerin, mannitol, potassium chloride, sodium chloride); Vehicle:flavored and/or sweetened (aromatic elixir, compound benzaldehydeelixir, iso-alcoholic elixir, peppermint water, sorbitol solution,syrup, tolu balsam syrup); Vehicle: oleaginous (almond oil, corn oil,cottonseed oil, ethyl oleate, isopropyl myristate, isopropyl palmitate,mineral oil, light mineral oil, myristyl alcohol, octyldodecanol, oliveoil, peanut oil, persic oil, sesame oil, soybean oil, squalane);Vehicle: solid carrier (sugar spheres); Vehicle: sterile (bacteriostaticwater for injection, bacteriostatic sodium chloride injection);Viscosity-increasing (see suspending agent); Water repelling agent(cyclomethicone, dimethicone, simethicone); and Wetting and/orsolubilizing agent (benzalkonium chloride, benzethonium chloride,cetylpyridinium chloride, docusate sodium, nonoxynol 9, nonoxynol 10,octoxynol 9, poloxamer, polyoxyl 35 castor oil, polyoxyl 40,hydrogenated castor oil, polyoxyl 50 stearate, polyoxyl 10 oleyl ether,polyoxyl 20, cetostearyl ether, polyoxyl 40 stearate, polysorbate 20,polysorbate 40, polysorbate 60, polysorbate 80, sodium lauryl sulfate,sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate,sorbitan monostearate, tyloxapol) may be used as excipients. This listis not meant to be exclusive, but instead merely representative of theclasses of excipients and the particular excipients which may be used indosage forms of the present disclosure.

Illustrative pharmaceutical compositions are tablets and gelatincapsules comprising a Compound of the Disclosure and a pharmaceuticallyacceptable carrier, such as a) a diluent, e.g., purified water,triglyceride oils, such as hydrogenated or partially hydrogenatedvegetable oil, or mixtures thereof, corn oil, olive oil, sunflower oil,safflower oil, fish oils, such as EPA or DHA, or their esters ortriglycerides or mixtures thereof, omega-3 fatty acids or derivativesthereof, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose,sodium, saccharin, glucose and/or glycine; b) a lubricant, e.g., silica,talcum, stearic acid, its magnesium or calcium salt, sodium oleate,sodium stearate, magnesium stearate, sodium benzoate, sodium acetate,sodium chloride and/or polyethylene glycol; for tablets also; c) abinder, e.g., magnesium aluminum silicate, starch paste, gelatin,tragacanth, methylcellulose, sodium carboxymethylcellulose, magnesiumcarbonate, natural sugars such as glucose or beta-lactose, cornsweeteners, natural and synthetic gums such as acacia, tragacanth orsodium alginate, waxes and/or polyvinylpyrrolidone, if desired; d) adisintegrant, e.g., starches, agar, methyl cellulose, bentonite, xanthangum, algic acid or its sodium salt, or effervescent mixtures; e)absorbent, colorant, flavorant and sweetener; f) an emulsifier ordispersing agent, such as Tween 80, Labrasol, HPMC, DOSS, caproyl 909,labrafac, labrafil, peceol, transcutol, capmul MCM, capmul PG-12, captex355, gelucire, vitamin E TGPS or other acceptable emulsifier; and/or g)an agent that enhances absorption of the compound such as cyclodextrin,hydroxypropyl-cyclodextrin, PEG400, PEG200.

For preparing pharmaceutical compositions from the compounds describedin this disclosure inert, pharmaceutically acceptable carriers can beeither solid or liquid. The powders and tablets may be comprised of fromabout 5 to about 95 percent active ingredient. Suitable solid carriersare known in the art, e.g., magnesium carbonate, magnesium stearate,talc, sugar or lactose. Tablets, powders, cachets and capsules can beused as solid dosage forms suitable for oral administration. Examples ofpharmaceutically acceptable carriers and methods of manufacture forvarious compositions may be found in A. Gennaro (ed.), Remington'sPharmaceutical Sciences, 18th Edition, (1990), Mack Publishing Co.,Easton, Pa.

Since the compounds of this disclosure are intended for use inpharmaceutical compositions a skilled artisan will understand that theycan be provided in substantially pure forms for example, at least 60%pure, more suitably at least 75% pure, preferably at least 85% pure andmost preferably at least 98% pure (w/w).

The pharmaceutical preparation may be in a unit dosage form. In suchform, the preparation is subdivided into suitably sized unit dosescontaining appropriate quantities of the active component, e.g., aneffective amount to achieve the desired purpose.

The quantity of active compound in a unit dose of preparation may bevaried or adjusted from about 1 mg to about 1000 mg, from about 1 mg toabout 500 mg, from about 1 mg to about 250 mg, or from about 1 mg toabout 25 mg, according to the particular application.

The CBP Inhibitor Compounds provided herein are preferably administeredin a therapeutically effective amount (e.g., an amount having a suitablefavorable therapeutic index). The amount and frequency of administrationof the compounds of the disclosure and/or the pharmaceuticallyacceptable salts thereof will be regulated according to the judgment ofthe attending clinician considering such factors as age, condition andsize of the patient as well as severity of the medical condition beingtreated. The dosage regimen utilizing the disclosed compound is selectedin accordance with a variety of factors including type, species, age,weight, sex and medical condition of the patient; the severity of thecondition to be treated; the route of administration; the renal orhepatic function of the patient; and the particular disclosed compoundemployed. A physician or veterinarian of ordinary skill in the art canreadily determine and prescribe the effective amount of the drugrequired to prevent, counter or arrest the progress of the condition.

The actual dosage employed may be varied depending upon the requirementsof the patient and the severity of the condition being treated.Determination of the proper dosage regimen for a particular situation iswithin the skill of the art. For convenience, the total daily dosage maybe divided and administered in portions during the day as required.Effective dosage amounts of the disclosed compounds, when used for theindicated effects, range from about 0.5 mg to about 5000 mg of thedisclosed compound as needed to treat the condition. Compositions for invivo or in vitro use can contain about 0.5, 5, 20, 50, 75, 100, 150,250, 500, 750, 1000, 1250, 2500, 3500, or 5000 mg of the disclosedcompound, or, in a range of from one amount to another amount in thelist of doses.

The compounds of Formula (I) can form salts (e.g., pharmaceuticallyacceptable salts) which are also within the scope of this disclosure.Reference to a compound of the Formula herein is understood to includereference to salts thereof, unless otherwise indicated.

All such acid salts and base salts are intended to be pharmaceuticallyacceptable salts within the scope of the disclosure and all acid andbase salts are considered equivalent to the free forms of thecorresponding compounds for purposes of the disclosure.

The following numbered embodiments, while non-limiting, are exemplary ofcertain aspects of the present disclosure:

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof,

wherein:

R¹ is —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, or —OR⁵;

R² is —H, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, or aryl, wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R⁶, andwherein a —C₁-C₆alkyl group may have one or more methylene unitsreplaced by —NR⁶—, —O— or —S—;

R³ is —H, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl,heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R⁷; R⁴and R^(4′) are each independently —H, halogen, —OH, —CN, or —NH₂;

R⁵ is —C₁-C₆alkyl, —C₃-C₈cycloalkyl, heterocyclyl, aryl, or heteroaryl;

R⁶ and R⁷ are each independently, at each occurrence, —H, —C₁-C₆alkyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, heteroaryl, —OH, halogen, oxo, —CN,—SR⁸, —OR⁸, —(CH₂)_(n)—OR⁸, —NHR⁸, —NR⁸R⁹, —S(O)₂NR⁸R⁹, —S(O)₂R^(8′),—C(O)R^(8′), —C(O)OR⁸, —C(O)NR⁸R⁹, —NR⁸C(O)R^(9′), —NR⁸S(O)₂R^(9′),—S(O)R^(8′), —S(O)NR⁸R⁹, or —NR⁸S(O)R^(9′), wherein each alkyl,cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl,heteroaryl, or aryl is optionally substituted with one or more R¹⁰;

wherein any two R⁶ or any two R⁷, when on non-adjacent atoms, cancombine to form a bridging cycloalkyl or heterocyclyl;

wherein any two R⁶ or any two R⁷, when on adjacent atoms, can combine toform a cycloalkyl, heterocyclyl, aryl or heteroaryl;

R⁸ and R⁹ are each independently, at each occurrence, —H, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl isoptionally substituted with one or more R¹⁰ or R¹¹; or

R⁸ and R⁹ may combine with the atom to which they are both attached toform a —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰ or R¹¹;

R^(8′) and R^(9′) are each independently, at each occurrence,—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl,alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, orheteroaryl is optionally substituted with one or more R¹⁰ or R¹¹; or

R⁸ and R^(9′) may combine with the atom to which they are both attachedto form a —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰ or R¹¹;

R¹⁰ and R¹¹ are each independently, at each occurrence, —H, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂,—OC₁-C₆alkyl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl),—S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein each alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more —R²;

wherein any two R¹⁰ or any two R¹¹, when on non-adjacent atoms, cancombine to form a bridging cycloalkyl or heterocyclyl;

wherein any two R¹⁰ or any two R¹¹, when on adjacent atoms, can combineto form a cycloalkyl, heterocyclyl, aryl or heteroaryl;

R¹² is independently, at each occurrence, —H, —C₁-C₆alkyl,—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂,—OC₁-C₆alkyl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl),—S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂,—C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl,—N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl); and

n is an integer from 1 to 4.

2. The compound of embodiment 1, wherein R¹ is —OR⁵ or —C₁-C₆alkyl.3. The compound of embodiment 2, wherein R⁵ is —C₁-C₆alkyl.4. The compound of embodiment 2, wherein R¹ is —OCH₃.5. The compound of embodiment 2, wherein R¹ is —C₁-C₆alkyl.6. The compound any one of embodiments 1-5, wherein R³ is —C₁-C₆alkyl.7. The compound of any one of embodiments 1-5, wherein R³ isheterocyclyl optionally substituted with one or more R⁷.8. The compound of any one of embodiments 1-5, wherein R³ is heteroaryloptionally substituted with one or more R⁷.9. The compound of any one of embodiments 1-5, wherein R³ isspirocycloalkyl optionally substituted with one or more R⁷.10. The compound of any one of embodiments 1-5, wherein R³ isspiroheterocyclyl optionally substituted with one or more R⁷.11. The compound of any one of embodiments 1-5, wherein R³ isC₃-C₈cycloalkyl optionally substituted with one or more R⁷.12. The compound of any one of embodiments 1-5, wherein R³ is aryloptionally substituted with one or more R⁷.13. The compound of any one of embodiments 1-5, wherein R³ iscyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl optionallysubstituted with one or more —R⁷.14. The compound of any one of embodiments 1-5, wherein R³ iscyclopentyl optionally substituted with one or more —R⁷.15. The compound of any one of embodiments 1-5, wherein R³ is cyclohexyloptionally substituted with one or more —R⁷.16. The compound of any one of embodiments 1-5, wherein R³ iscyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl optionallysubstituted with one or more —S(O)₂NH₂, —C(O)OH, —C(O)NH₂, or —S(O)NH₂.17. The compound of any one of embodiments 1-16, wherein R² isC₁-C₆alkyl optionally substituted with one or more R⁶.18. The compound of any one of embodiments 1-16, wherein R² is aryloptionally substituted with one or more R⁶.19. The compound of any one of embodiments 1-16, wherein R² isC₃-C₈cycloalkyl optionally substituted with one or more R⁶.20. The compound of any one of embodiments 1-16, wherein R² isC₁-C₂alkyl substituted with aryl or heteroaryl, wherein each aryl orheteroaryl is optionally substituted with one or more R¹⁰.21. The compound of embodiment 1, wherein R² is C₁-C₂alkyl substitutedwith aryl or heteroaryl, wherein each aryl or heteroaryl is optionallysubstituted with one or more R¹⁰; and wherein R³ is cyclohexyloptionally substituted with one or more —S(O)₂NH₂, —C(O)OH, —C(O)NH₂, or—S(O)NH₂.22. The compound of any one of embodiments 1 or 6-21, wherein R¹ is—C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, heteroaryl, or aryl.23. The compound of embodiment 1 having the Formula (I-a):

or a pharmaceutically acceptable salt thereof,wherein Ring A representsa —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heteroaryl, or aryl.

24. The compound of embodiment 1 having the Formula (I-b):

or a pharmaceutically acceptable salt thereof, wherein Ring B representsa —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heteroaryl, or aryl.

25. The compound of embodiment 1 having the Formula (I-c):

or a pharmaceutically acceptable salt thereof, wherein m is an integerfrom 1 to 4.

26. The compound of embodiment 1 having the Formula (I-d):

or a pharmaceutically acceptable salt thereof,wherein Ring B represents—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, or heteroaryl, and

wherein p is an integer from 1 to 2.

27. The compound of embodiment 26, wherein Ring B is —C₃-C₈cycloalkyl.28. The compound of embodiment 26, wherein Ring B is —C₄-C₈cycloalkenyl.29. The compound of embodiment 26, wherein Ring B is aryl.30. The compound of embodiment 26, wherein Ring B is heterocyclyl.31. The compound of embodiment 26, wherein Ring B is heteroaryl.32. The compound of embodiment 1 having the Formula (I-f):

-   -   or a pharmaceutically acceptable salt thereof, wherein Ring B        is-C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,        spirocycloalkyl, spiroheterocyclyl, or heteroaryl; and    -   L is a C₁-C₆ alkylene chain optionally substituted with one or        more R⁶; or    -   L is a C₁-C₆ alkylene chain optionally substituted with one or        more R⁶, and wherein at least one methylene unit of L is        replaced by —NR⁶—, —O— or —S—.        33. The compound of embodiment 32, wherein Ring B is        —C₃-C₈cycloalkyl.        34. The compound of embodiment 32, wherein Ring B is        —C₄-C₈cycloalkenyl.        35. The compound of embodiment 32, wherein Ring B is aryl.        36. The compound of embodiment 32, wherein Ring B is        heterocyclyl.        37. The compound of embodiment 32, wherein Ring B is heteroaryl.        38. The compound of any of embodiments 33-37, wherein L is a        C₁-C₆ alkylene chain optionally substituted with one or more R⁶.        39. The compound of any one of embodiments 33-37, wherein L is        C₁-C₂ alkylene.        40. The compound of any of embodiments 33-37, wherein L is a        C₁-C₆ alkylene chain optionally substituted with one or more R⁶,        and wherein at least one methylene unit is replaced by —NR—, —O—        or —S—.        41. The compound of embodiment 40, wherein L is a C₁-C₆ alkylene        chain optionally substituted with one or more R⁶, and wherein at        least one methylene unit of L is replaced by —NR⁶.        42. The compound of embodiment 40, wherein L is a C₁-C₆ alkylene        chain optionally substituted with one or more R⁶, and wherein at        least one methylene unit of L is replaced by —O—.        43. The compound of embodiment 40, wherein L is a C₁-C₆ alkylene        chain optionally substituted with one or more R⁶, and wherein at        least one methylene unit of L is replaced by —S—.        44. The compound of embodiment 38, wherein R⁶ is —C(O)OH.        45. The compound of embodiment 44, wherein R³ is        —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl, or        heteroaryl.        46. The compound of embodiment 45, wherein R³ is cyclopentyl,        cyclohexyl, 3-pyranyl, or 4-pyranyl.        47. The compound of embodiment 46, wherein R³ is cyclopentyl,        cyclohexyl or 3-pyranyl.        48. The compound of embodiment 32, wherein L is an C₁-C₆        alkylene chain optionally substituted with one or more R⁶, and        wherein at least one methylene unit is replaced by —NR⁶—, —O— or        —S—; and

R³ is —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl, orheteroaryl, wherein each —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, or heteroaryl is optionally substituted with one ormore R⁷; and

R⁶ is independently, at each occurrence, —H, —C₁-C₆alkyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,spirocycloalkyl, spiroheterocyclyl, heteroaryl, —OH, halogen, oxo, —CN,—SR⁸, —OR⁸, —(CH₂)_(n)—OR⁸, —NHR⁸, —NR⁸R⁹, —S(O)₂NR⁸R⁹, —S(O)₂R^(8′),—C(O)R^(8′), —C(O)NR⁸R⁹, —NR⁸C(O)R^(9′), —NR⁸S(O)₂R^(9′), —S(O)R^(8′),—S(O)NR⁸R⁹, or —NR⁸S(O)R^(9′), wherein each alkyl, cycloalkyl,heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more R¹⁰;

wherein R¹⁰ is —H, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl,halogen, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl,—C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂,—C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl),—S(O)N(C₁-C₆alkyl)₂, or —N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl,heteroaryl, or aryl.

49. The compound of embodiment 48, wherein L is a C₁-C₆ alkylene chain,—OCH₂—, —CH₂O—, —NR⁶CH₂—, or —CH₂NR⁶—; and R⁶ is H, —C₁-C₆alkyl,—C₃-C₆cycloalkyl or —C(O)NR⁸R⁹.50. The compound of embodiment 48, wherein R³ is cyclopentyl orcyclohexyl, wherein each cyclopentyl or cyclohxyl is optionallysubstituted with R⁷.51. The compound of embodiment 50, wherein R⁷ is —OH, halogen, oxo, —CN,—SH, —OH, —NH₂, —S(O)₂NH₂, —C(O)OH, or —C(O)NH₂.52. The compound of embodiment 1 having the Formula (I-g):

53. The compound of embodiment 1 having the Formula (I-h):

or a pharmaceutically acceptable salt thereof.

54. The compound of embodiment 1 having the Formula (I-h′):

or a pharmaceutically acceptable salt thereof.

55. The compound of embodiment 1 having the Formula (I-h″)

or a pharmaceutically acceptable salt thereof.

56. The compound of embodiment 1 having the Formula (I-e):

or a pharmaceutically acceptable salt thereof, wherein p is 1 or 2.

57. The compound of embodiment 56, wherein p is 1.58. The compound of embodiment 56, wherein p is 2.59. The compound of embodiment 56, wherein R⁷ is —C(O)OH.60. The compound of embodiment 56, wherein R⁶ is aryl or heteroaryl,wherein each aryl or heteroaryl is optionally substituted with one ormore R¹⁰.61. A compound of any one of embodiments 1-60 for use in the manufactureof a medicament for treating a disease associated with inhibiting one ormore of CBP/p300-family bromodomains.62. A compound of any one of embodiments 1-60 for use in the manufactureof a medicament for treating a disease or disorder in a patient in needthereof.63. Use of a compound of any one of embodiments 1-60 in the treatment ofa disease associated with inhibiting one or more of CBP/p300-familybromodomains.64. Use of a compound of any one of embodiments 1-60 in the treatment ofa disease or disorder in a patient in need thereof.

EXAMPLES

Definitions used in the following Schemes and elsewhere herein are:

-   ACN acetonitrile-   Ac₂O acetic anhydride-   (±)BINAP (±)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthalen-   Boc tert-butoxycarbonyl-   Brettphos    Dicyclohexyl[3,6-dimethoxy-2′,4′,6′-tris(1-methylethyl)[1,1′-biphenyl]-2-yl]phosphine-   Brettphos Pd G3 or 3^(rd) generation BrettPhos precatalyst:    Methanesulfonato(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-tri-i-propyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II)-   n-BuOH butanol-   cm centimeter-   DCE 1,2-dichloroethane-   DCM dichloromethane or methylene chloride-   D-CSA D-Camphorsulfonic acid-   DEA diethylamine-   DMC 2-Chloro-4,5-dihydro-1,3-dimethyl-1H-imidazolium chloride-   DMP Dess-Martin periodinane,    1,1,1-Tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one-   DMTMM 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium    chloride-   DIEA N,N-diisopropylethylamine-   DMAP 4-(dimethylamino)pyridine-   DMF N,N-dimethylformamide-   DMSO dimethylsulfoxide-   DPPA diphenylphosphoryl azide-   dppf bis(diphenylphosphino)ferrocene-   EDC 1-Ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride-   ES electrospray ionization-   Et₃N triethylamine-   EtOAc ethyl acetate-   EtOH ethanol-   FA formic acid-   FCC flash column chromatography-   h hours-   HATU    2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium    hexafluorophosphate-   HCl hydrogen chloride-   HOAc acetic acid-   HPLC high performance liquid chromatography-   [Ir(COD)Cl]₂ chloro(1,5-cyclooctadiene)iridium(I) dimer-   (i-Pr)₂NEt N,N-diisopropylethylamine-   L liter-   LC/MS liquid chromatography/mass spectrometry-   LCMS liquid chromatography/mass spectrometry-   LDA lithium diisopropylamine-   LRMS low resolution mass spectrometry-   K₂CO₃ potassium carbonate-   KHMDS Potassium hexamethyldisilazide-   mCPBA 3-Chloroperoxybenzoic acid-   MeOH methanol-   mL milliliter-   mmol millimole-   mg milligram-   MHz megahertz-   MS mass spectrometry-   m/z mass/charge ratio-   NBS N-bromosuccinimide-   nm nanometer-   NMM 4-methylmorpholine-   NMR nuclear magnetic resonance-   NH₄Cl ammonium chloride-   Pd₂(dba)₃ tris(dibenzylideneacetone)dipalladium-   Ph₃P triphenylphosphine-   PhCHO benzaldehyde-   PhMe toluene-   ppm parts per million-   rt room temperature-   RT rentention time-   (S)-(−)-MeO-BIPHEP    (S)-(−)-2,2′-Bis(diphenylphosphino)-6,6′-dimethoxy-1,1′-biphenyl-   SFC supercritical fluid chromatography-   STAB sodium triacetoxyborohydride-   TBS tert-Butyldimethylsilyl-   TBDMS tert-Butyldimethylsilyl chloride-   p-TSA para-toluenesulfonic anhydride-   p-TsOH para-toluenesulfonic acid-   TFA trifluoroacetic acid-   TFAA trifluoroacetic anhydride-   THE tetrahydrofuran-   TMSCN trimethylsilyl cyanide-   UV ultraviolet-   XPhos 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl-   ZnI₂ zinc iodide

Materials

Unless otherwise noted, all materials were obtained from commercialsuppliers and were used without further purification. Anhydrous solventswere obtained from Sigma-Aldrich (Milwaukee, Wis.) and used directly.All reactions involving air- or moisture-sensitive reagents wereperformed under a nitrogen atmosphere and all reactions utilizingmicrowave irraditation were run on a Biotage Initiator EXP EUinstrument.

Unless otherwise noted, mass-triggered HPLC purification and/or purityand low resolution mass spectral data were measured using either: (1)Waters Acquity ultra performance liquid chromatography (UPLC) system(Waters Acquity UPLC with Sample Organizer and Waters Micromass ZQ MassSpectrometer) with UV detection at 220 nm and a low resonanceelectrospray positive ion mode (ESI) (Column: Acquity UPLC BEH C18 1.7μm 2.1×50 mm; gradient: 5-100% Solvent B (95/5/0.09%:Acetonitrile/Water/Formic Acid) in Solvent A (95/5/0.1%: 10 mM AmmoniumFormate/Acetonitrile/Formic Acid) for 2.2 min then 100-5% Solvent B inSolvent A for 0.01 min then hold at 5% Solvent B in Solvent A for 0.29min) or (2) Waters HT2790 Alliance high performance liquidchromatography (HPLC) system (Waters 996 PDA and Waters ZQ Single QuadMass Spectrometer) with UV detection at 220 nm and 254 nm and a lowresonance electrospray ionization (positive/negative) mode (ESI)(Column: XBridge Phenyl or C18, 5 μm 4.6×50 mm; gradient: 5-95% SolventB (95% methanol/5% water with 0.1% Formic Acid) in Solvent A (95%water/5% methanol with 0.1% Formic Acid) for 2.5 min then hold at 95%Solvent B in Solvent A for 1 min (purity and low resolution MS only).

General Methods of Compound Preparation

Described herein are methods of synthesizing the compounds of thepresent disclosure. Compounds of the present disclosure can besynthesized according to the synthetic schemes provided below.Preparation of the starting material for Schemes 1 and 2 is described in“Preparation of Intermediates,” see Intermediate 1. Preparation of thestarting material for Schemes 3 and 4 can be found in Example 1, Part Aof U.S. Pat. No. 4,404,207.

Unless otherwise specified, the substituents R² and R³ and of thefollowing reaction schemes are as defined in the description and claims.

Scheme 1 provides methods useful for synthesizing compounds of FormulaI.

Scheme 2 provides methods useful for synthesizing compounds of FormulaI.

Alternatively, Scheme 3 provides methods useful for synthesizing certaincompounds of Formula I.

Alternatively, Scheme 4 provides methods useful for synthesizing certaincompounds of Formula I.

Unless otherwise specified, Ring B, R¹, R⁶, R⁷, R¹⁰, m and q and of thefollowing reaction schemes are as defined in the description and claims.The compounds described herein may be made from commercially availablestarting materials or synthesized using known organic, inorganic, and/orenzymatic processes. For example, 6-fluoro-2-methylquinoline can benitrated under acidic conditions to afford6-fluoro-2-methyl-5-nitroquinoline. Asymmetric iridium-catalyzedhydrogenation of the quinoline gives(S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline. Carbamateformation and subsequent nucleophilic aromatic substitution yields amethyl 6-fluoro-2-methyl-5-nitroquinoline. Nitro reduction, acylationand acid-mediated cyclization yields the methyl(S)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylatecore of Formula I-i.

Scheme 5 provides methods useful for synthesizing certain compounds ofFormula I-i.

Preparation of Intermediates Intermediate 1: methyl(S)-5-amino-6-bromo-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Step 1. 8-chloro-5-methoxy-2-methylquinoline hydrochloride

Into a 5 L 4-necked round-bottom flask purged and maintained with aninert atmosphere of nitrogen, 2-chloro-5-methoxyaniline (250 g, 1.59mol) was dissolved in 1-butanol (1200 mL). Then hydrochloric acid (aq,36.5%, 526.5 mL) and chloranil (456.5 g, 1.86 mol) were added. Theresulting mixture was stirred for 1 h at 100° C. under nitrogenatmosphere. Then a solution of (E)-but-2-enal (169 mL, 2.06 mol) in1-butanol (300 mL) was added dropwise. The resulting solution wasstirred for 1 h at 100° C. under nitrogen atmosphere. The oil bath wascooled to 70° C. and tetrahydrofuran (1500 mL) was added. Then theresulting mixture was stirred for 1 h at 70° C. The reaction mixture wascooled to 0° C. and the solids were filtered. The solids were washedwith tetrahydrofuran (3 L) at 0° C. This afforded the title compound(300 g, 77%) as a yellow solid. MS: (ES, m/z): 208, 210 [M+H]⁺.

Step 2. 5-methoxy-2-methylquinoline

Into a 1000-mL 3-necked round-bottom flask,8-chloro-5-methoxy-2-methylquinoline hydrochloride (50 g, 204.82 mmol)was dissolved in methanol (300 mL). Then sodium hydroxide (3M, 205 mL)and 10% palladium on carbon (25 g) were added. Hydrogen (g) was chargedinto the reaction mixture. The reaction mixture was stirred under ahydrogen atmosphere for 3 h at room temperature. The reaction was ventedto nitrogen and the solids were filtered out over celite. The filteredsolution was concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (1:5).This afforded the title compound (28.5 g, 80%) as a yellow oil. MS: (ES,m/z): 174 [M+H]⁺.

Step 3. (2S)-5-methoxy-2-methyl-1,2,3,4-tetrahydroquinoline

Into a 30-mL pressure tank reactor (50 atm), 5-methoxy-2-methylquinoline(4.0 g, 23.09 mmol) was dissolved in methanol (10 mL). ThenRu(OTf)(η6-hexamethylbenzene)((S,S)-TsDPEN)([N-[(1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN][(1,2,3,4,5,6-η)-1,2,3,4,5,6-hexamethylbenzene](1,1,1-trifluoromethanesulfonato-κO)-ruthenium,prepared according to the procedure in J. Am. Chem. Soc. 2011, 133,9878-9891 (150 mg, 0.23 mmol) was added. To the above hydrogen wasintroduced in. The resulting solution was stirred for 20 h at roomtemperature. The resulting mixture was concentrated under vacuum. Theresidue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:4). This afforded the title compound (3.0 g,73%) as a yellow oil. MS: (ES, m/z): 178 [M+H]⁺.

Step 4. methyl(S)-5-methoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 250-mL round-bottom flask,(2S)-5-methoxy-2-methyl-1,2,3,4-tetrahydroquinoline (18 g, 99.52 mmol)was dissolved in dichloromethane (100 mL). Then pyridine (23.6 g, 298.36mmol) was added, followed by methyl carbonochloridate (9.4 g, 99.47mmol). The resulting solution was stirred for 1 h at room temperature.The resulting solution was diluted with 100 mL of dichloromethane andwashed with 3×200 mL of water. The organic layers were combined, driedover anhydrous sodium sulfate, filtered and concentrated under vacuum.The residue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:3). This afforded the title compound (21 g,89%) as a yellow oil. MS: (ES, m/z): 236 [M+H]⁺.

Step 5. methyl(S)-5-hydroxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 500-mL 3-necked round-bottom flask, methyl(2S)-5-methoxy-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate (21 g,89.36 mmol) was dissolved in dichloromethane (150 mL). Then borontribromide (150 mL, 0.15 mol, 1 M in CH₂Cl₂) was added. The resultingsolution was stirred for 1 h at room temperature. The reaction was thenquenched by the addition of 300 mL of water. The resulting mixture wasextracted with 3×300 mL of dichloromethane. The organic layers werecombined, dried over anhydrous sodium sulfate, filtered and concentratedunder vacuum. The residue was subjected to purification by FCC elutingwith ethyl acetate/petroleum ether (1:2). This afforded the titlecompound (13.5 g, 68%) as a yellow solid. MS: (ES, m/z): 222 [M+H]⁺.

Step 6. methyl(S)-2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 250-mL round-bottom flask, methyl(2S)-5-hydroxy-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate (5 g,18.08 mmol) was dissolved in dichloromethane (50 mL). Then pyridine(14.3 g, 180.78 mmol) and trifluoromethanesulfonic anhydride (10.2 g,36.15 mmol) were added. The resulting solution was stirred for 1 h atroom temperature. The resulting mixture was washed with 3×100 mL ofwater. The organic layers were combined, dried over anhydrous sodiumsulfate, filtered and concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:3). This afforded the title compound (5.5 g, 86%) as a yellowoil. MS: (ES, m/z): 354 [M+H]⁺.

Step 7. methyl(S)-5-((diphenylmethylene)amino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 500-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-2-methyl-5-[(trifluoromethane)sulfonyloxy]-1,2,3,4-tetrahydroquinoline-1-carboxylate(23.5 g, 65.18 mmol) was dissolved in toluene (100 mL). Thendiphenylmethanimine (17.9 g, 97.78 mmol),tris(dibenzylideneacetone)dipalladium-chloroform adduct (1.19 g, 1.30mmol), (+/−)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (2.43 g, 3.90mmol) and cesium carbonate (42.4 g, 130.13 mmol) were added. Theresulting solution was stirred overnight at 100° C. under nitrogenatmosphere. The reaction mixture was cooled and the solids were filteredout. The residue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:3). This afforded the title compound (33 g,80%) as a yellow oil. MS: (ES, m/z): 385 [M+H]⁺.

Step 8. methyl(S)-5-amino-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 500-mL round-bottom flask, methyl(2S)-5-[(diphenylmethylidene)amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(33 g, 85.93 mmol) was dissolved in methanol (200 mL). Then sodiumacetate (17 g, 207.23 mmol) and hydroxylamine hydrochloride (12.3 g,177.00 mmol) were added. The resulting solution was stirred for 2 h atroom temperature. The solids were filtered out. The resulting mixturewas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (1:2). This affordedthe title compound (12.5 g, 66%) as a yellow solid. MS: (ES, m/z): 221[M+H]⁺.

Step 9. methyl(S)-5-amino-6-bromo-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate(Intermediate 1)

Into a 100-mL 3-necked round-bottom flask, methyl(2S)-5-amino-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate (1 g,4.09 mmol) was dissolved in acetonitrile (20 mL). ThenN-bromosuccinimide (730 mg, 4.10 mmol) was added. The resulting solutionwas stirred for 30 min at room temperature. The resulting mixture wasconcentrated under vacuum. The residue was subjected to purification byFCC eluting with ethyl acetate/petroleum ether (1:1). This afforded thetitle compound (1.1 g, 90%) as a yellow solid. MS: (ES, m/z): 299, 301[M+H]⁺.

H-NMR: (400 MHz, CD3OD, ppm): 7.19 (d, J=8.8 Hz, 1H), 6.84 (d, J=8.8 Hz,1H), 4.73-4.69 (m, 1H), 3.74 (s, 3H), 2.64-2.57 (m, 1H), 2.55-2.44 (m,1H), 2.12-2.05 (m, 1H), 1.82-1.79 (m, 1H), 1.17 (d, J=6.9 Hz, 3H).

Intermediate 2: 3-phenylbutanoyl chloride

Into a 25-mL round-bottom flask, 3-phenylbutanoic acid (50 mg, 0.30mmol) was dissolved in dichloromethane (5 mL). Then oxalyl chloride (2mL) and one drop of N, N-dimethylformamide were added. The resultingsolution was stirred for 3 h at room temperature. The resulting mixturewas concentrated under vacuum. This afforded the title compound (51 mg,90%) as yellow oil.

Intermediates 3 and 4: ethyl(trans)-4-amino-1-methylcyclohexane-1-carboxylate and ethyl(cis)-4-amino-1-methylcyclohexane-1-carboxylate

Step 1. Synthesis of ethyl 1,4-dioxaspiro[4.5]decane-8-carboxylate

Into a 250-mL round-bottom flask, ethyl 4-oxocyclohexane-1-carboxylate(10 g, 58.75 mmol) was dissolved in toluene (100 mL). Thenethane-1,2-diol (14.60 g, 235.23 mmol) was added, followed byp-toluenesulfonic acid (1.02 g, 5.92 mmol). The resulting solution wasstirred for 14 h at 100° C. After cooled to room temperature, theresulting solution was diluted with 100 mL of water. The resultingsolution was extracted with 3×100 mL of ethyl acetate. The organiclayers were combined and washed with 3×100 mL of saturated sodiumbicarbonate. The organic layer was dried over anhydrous sodium sulfate,filtered and concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether(5:1).This afforded the title compound (3.0 g, 23%) as a yellow oil. MS:(ES, m/z): 215 [M+H]⁺.

Step 2. Synthesis of ethyl8-methyl-1,4-dioxaspiro[4.5]decane-8-carboxylate

Into a 250-mL 3-necked round-bottom flask, ethyl1,4-dioxaspiro[4.5]decane-8-carboxylate (2.4 g, 11.20 mmol) wasdissolved in tetrahydrofuran (100 mL). Then lithium diisopropylamide (2Min tetrahydrofuran, 8.4 mL, 16.77 mmol) was added dropwise. The mixturewas stirred for 30 min at −78° C. To this was added iodomethane (2.38 g,16.77 mmol). The resulting solution was stirred for 1 h at −78° C. Thereaction was then quenched by the addition of 100 mL of ammoniumchloride (aq, sat) and extracted with 3×100 ml of ethyl acetate. Theorganic layers were combined, dried over sodium sulfate, filtered andconcentrated under vacuum. The residue was subjected to purification byFCC eluting with ethyl acetate/petroleum ether (1:2). This afforded thetitle compound (1.8 g, 69%) as a yellow oil. MS: (ES, m/z): 229 [M+H]⁺.

Step 3. Synthesis of ethyl 1-methyl-4-oxocyclohexane-1-carboxylate

Into a 100-mL round-bottom flask, ethyl8-methyl-1,4-dioxaspiro[4.5]decane-8-carboxylate (2.3 g, 10.08 mmol) wasdissolved in acetone (20 mL). Then sulfuric acid (1M, 20 mL) was added.The resulting solution was stirred for 14 h at room temperature. Theresulting solution was diluted with 50 ml of water and extracted with3×50 ml of ethyl acetate. The organic layers were combined, dried oversodium sulfate, filtered and concentrated under vacuum. This affordedthe title compound (1.8 g, crude) as a yellow oil. MS: (ES, m/z): 185[M+H]⁺.

Step 4. Synthesis of ethyl(trans)-4-(benzylamino)-1-methylcyclohexane-1-carboxylate and ethyl(cis)-4-(benzylamino)-1-methylcyclohexane-1-carboxylate

Into a 100-mL round-bottom flask, ethyl1-methyl-4-oxocyclohexane-1-carboxylate (1.7 g, 9.99 mmol) was dissolvedin methanol (20 mL). Benzylamine (1.2 g, 11.20 mmol) and acetic acid(2.8 g, 46.63 mmol) were added, followed by sodium cyanoborohydride (2.9g, 46.15 mmol). The resulting solution was stirred for 3 h at roomtemperature. The resulting solution was diluted with 30 mL of water andextracted with 3×30 mL of ethyl acetate. The organic layers werecombined, dried over anhydrous sodium sulfate, filtered and concentratedunder vacuum. The crude product was purified by Prep-SFC with thefollowing conditions: Column, Chiralpak AD-H, 2×25 cm (5 um); mobilephase, CO₂ (80%), MeOH (2 mM NH₃-MeOH)(20%); Flow rate: 40 mL/min;Detector, UV 220 nm. This afforded the title compounds as follows: 280mg (11%) of ethyl(trans)-4-(benzylamino)-1-methylcyclohexane-1-carboxylate (assumedstereochemistry, first eluting isomer, RT=3.75 min) as a yellow solidand 350 mg (13%) of ethyl(cis)-4-(benzylamino)-1-methylcyclohexane-1-carboxylate (assumedstereochemistry, second eluting isomer, RT=4.74 min) as a yellow solid.MS: (ES, m/z): 276 [M+H]⁺.

Step 5. Synthesis of ethyl(trans)-4-amino-1-methylcyclohexane-1-carboxylate and ethyl(cis)-4-amino-1-methylcyclohexane-1-carboxylate

Into a 50-mL round-bottom flask, ethyltrans-4-(benzylamino)-1-methylcyclohexane-1-carboxylate (280 mg, 1.02mmol) or ethyl cis-4-(benzylamino)-1-methylcyclohexane-1-carboxylate(280 mg, 1.02 mmol) was dissolved in methanol (10 mL). Palladium carbon(280 mg, 10%) was added. Hydrogen (g) was introduced into the reactionmixture. The resulting solution was stirred for 5 h at room temperatureunder hydrogen atmosphere. The solids were filtered out and theresulting mixture was concentrated under vacuum. This afforded theindependent title compounds (75 mg, crude) as yellow oils. MS: (ES,m/z): 186 [M+H]⁺.

Intermediate 5: 2-(3-fluoro-4-methoxyphenyl)acetaldehyde

Step 1. Synthesis of 2-(3-fluoro-4-methoxyphenyl)ethan-1-ol

2-(3-fluoro-4-methoxyphenyl)acetic acid (400 mg, 2.17 mmol) wasdissolved in THF (4 mL). The reaction solution was cooled to 0° C.Lithium aluminium hydride (90.8 mg, 2.39 mmol) was added portionwise.The flask was then wrapped with aluminum foil and the resulting solutionwas stirred for 1 h at room temperature. The reaction was then quenchedby the addition of 2 mL of water/ice. The resulting mixture wasconcentrated under vacuum. The solution was extracted with 2×10 mL ofethyl acetate and the organic layers were combined and evaporated. Thisafforded 290 mg (78%) of 2-(3-fluoro-4-methoxyphenyl)ethan-1-ol ascolorless oil.

Step 2. Synthesis of 2-(3-fluoro-4-methoxyphenyl)acetaldehyde

Into a 100-mL 3-necked round-bottom flask purged and maintained with aninert atmosphere of nitrogen, was placed2-(3-fluoro-4-methoxyphenyl)ethan-1-ol (290 mg, 1.70 mmol) indichloromethane (5 mL). The reaction was cooled to 0° C. and Dess-MartinPeriodinane (940 mg, 2.22 mmol, 1.30 equiv) was added. The flask waswrapped with aluminum foil and the resulting solution was stirred for 2h at room temperature. The resulting mixture was concentrated undervacuum. The residue was subjected to FCC eluting with ethylacetate/petroleum ether (1:5). This afforded the title compound (150 mg,52%) as a colorless oil. MS: (ES, m/z): 169 [M+H]⁺.

Intermediate 6: 3-(2H-1,2,3-triazol-2-yl)propanal

Step 1. Synthesis of 2-(3-fluoro-4-methoxyphenyl)acetaldehyde

1H-1,2,3-triazole (500 mg, 7.24 mmol) was dissolved in dichloromethane(15 mL) in a round bottom flask. Prop-2-enal (608 mg, 10.84 mmol) wasadded. The resulting solution was stirred for 1 h at room temperature.The resulting mixture was concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:2). This afforded the title compound (100 mg, 11%) as a yellowoil. MS: (ES, m/z): 126[M+H]⁺.

Intermediate 7: 3-(2-methyl-1,3-oxazol-5-yl)propanal

Step 1. Synthesis of (2-methyl-1,3-oxazol-5-yl)methanol

Into a 100-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, 2-methyl-1,3-oxazole-5-carboxylic acid (1.0 g,7.86 mmol) was dissolved in tetrahydrofuran (10 mL). Thenborane-tetrahydrofuran complex (31.6 mL, 330.2 mmol) was added dropwisewith stirring at 0° C. The resulting solution was stirred for 30 min at0° C. The resulting solution was allowed to react, with stirring, for anadditional 2 h at room temperature. The reaction was then quenched bythe addition of 20 mL of water and extracted with 3×40 mL of ethylacetate. The organic layers were combined, dried over anhydrous sodiumsulfate, filtered and concentrated under vacuum. This afforded the titlecompound (1.43 g, crude) as an off-white solid. MS: (ES, m/z): 114[M+H]⁺.

Step 2. Synthesis of 2-methyl-1,3-oxazole-5-carbaldehyde

Into a 25-mL round-bottom flask, (2-methyl-1,3-oxazol-5-yl)methanol(1.43 g, 12.6 mmol) was dissolved in dichloromethane (10 mL). Then(1,1,1-triacetoxy)-1,1-dihydro-1,2-benziodoxol-3(1H)-one (6.97 g, 16.44mmol) was added. The resulting solution was stirred for 30 min at 0° C.The resulting solution was allowed to react, with stirring, for anadditional 2 h at room temperature. The reaction was then quenched bythe addition of 20 mL of aqueous solution of sodium bicarbonate and 20mL of aqueous solution of sodium bisulfite. The resulting solution wasextracted with 3×30 mL of dichloromethane and the organic layers werecombined, dried over anhydrous sodium sulfate, filtered and concentratedunder vacuum. The residue was subjected to purification by FCC elutingwith ethyl acetate/petroleum ether (1:1). This afforded the titlecompound (677.3 mg, 48.4%) as an off-white solid. MS: (ES, m/z): 112[M+H]⁺.

Step 3. Synthesis of ethyl(2E)-3-(2-methyl-1,3-oxazol-5-yl)prop-2-enoate

Into a 250-mL 3-necked round-bottom flask purged and maintained with aninert atmosphere of nitrogen, ethyl 2-(diethoxyphosphoryl)acetate (3.55g, 15.9 mmol) was dissolved in tetrahydrofuran (20 mL). Then sodiumhydride (3.29 g, 60% in oil, 137.3 mmol) in tetrahydrofuran (2 mL) wasadded dropwise with stirring at 0° C. The resulting mixture was stirredfor 30 min at 0° C. To this was added a solution of2-methyl-1,3-oxazole-5-carbaldehyde (677.3 mg, 6.10 mmol) intetrahydrofuran (2 mL) dropwise with stirring at 0° C. The resultingsolution was stirred for 1.5 h at 0° C. The reaction was then quenchedby the addition of 40 mL of water and extracted with 3×80 mL of ethylacetate. The organic layers were combined, dried over anhydrous sodiumsulfate, filtered and concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:1). This afforded the title compound (145 mg, 13%) as a lightyellow liquid. MS: (ES, m/z): 182 [M+H]⁺.

Step 4. Synthesis of ethyl 3-(2-methyl-1,3-oxazol-5-yl)propanoate

Into a 25-mL round-bottom flask, ethyl(2E)-3-(2-methyl-1,3-oxazol-5-yl)prop-2-enoate (145 mg, 0.80 mmol) wasdissolved in methanol (5 mL). Then 10% palladium carbon (145 mg) wasadded. To the above hydrogen (g) was introduced in. The resultingsolution was stirred for 2 h at room temperature. The solids werefiltered out. The resulting mixture was concentrated under vacuum. Thisafforded the title compound (150 mg, crude) as a colorless oil. MS: (ES,m/z): 184 [M+H]⁺.

Step 5. Synthesis of 3-(2-methyl-1,3-oxazol-5-yl)propan-1-ol

Into a 25-mL 2-necked round-bottom flask purged and maintained with aninert atmosphere of nitrogen, ethyl3-(2-methyl-1,3-oxazol-5-yl)propanoate (134.2 mg, 0.73 mmol) wasdissolved in diethyl ether (5 mL). Then LAH (33.4 mg, 0.88 mmol) wasadded in portions at 0° C. The resulting solution was stirred for 1 h at0° C. The reaction was then quenched by the addition of 5 mL of aqueouspotassium sodium tartrate and extracted with 3×10 mL of ether. Theorganic layers were combined, dried over anhydrous sodium sulfate,filtered and concentrated under vacuum. This afforded the title compound(122 mg, crude) as a colorless oil. MS: (ES, m/z): 142 [M+H]⁺.

Step 6. Synthesis of 3-(2-methyl-1,3-oxazol-5-yl)propanal

Into a 25-mL round-bottom flask, 3-(2-methyl-1,3-oxazol-5-yl)propan-1-ol(122 mg, 0.86 mmol) was dissolved in dichloromethane (5 mL). Thendimethyl phthalate (980 mg, 2.31 mmol) was added at 0° C. The resultingsolution was stirred for 30 min at 0° C. The resulting solution wasallowed to react, with stirring, for an additional 2 h at roomtemperature. The resulting mixture was concentrated under vacuum. Theresidue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:1). This afforded the title compound (98.8mg, 82%) as a yellow solid. MS: (ES, m/z): 140 [M+H]⁺.

Intermediate 8: 3-(1-methyl-1H-pyrazol-4-yl)propanal

Into a 20-mL 2-necked round-bottom flask, was placed3-(1-methyl-1H-pyrazol-4-yl)propan-1-ol (140 mg, 1.00 mmol) indichloromethane (5 mL). Dess-Martin reagent (551 mg, 1.30 mmol) wasadded portionwise and the resulting solution was stirred for 1 h at roomtemperature. The resulting mixture was concentrated under vacuum. Theresidue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:1). This afforded the title compound as ayellow oil (110 mg, 80%). MS: (ES, m/z): 139 [M+H]⁺.

The following intermediates in TABLE A were prepared using standardchemical manipulations and procedures similar to those used for thepreparation of Intermediate 8.

TABLE A LRMS Intermediate m/z Number Structure and Compound Name [M +H]⁺  9

140 10

139 11

139 12

159 13

124 14

164 15

152 16

169 17

151 18

137 19

125

Intermediate 20: 3-(5-methyloxazol-2-yl)propanal

Step 1. Synthesis of 4-(benzyloxy)-N-(prop-2-yn-1-yl)butanamide

Into a 100-mL 3-necked round-bottom flask purged and maintained with aninert atmosphere of nitrogen, was placed 4-(benzyloxy)butanoic acid (515mg, 2.65 mmol) in DMF (5 mL). Prop-2-yn-1-amine (146 mg, 2.65 mmol),1H-1,2,3-benzotriazol-1-ol (358 mg, 2.65 mmol), and EDC (508 mg, 2.65mmol) were added. The flask was wrapped with aluminum foil and theresulting solution was stirred for 12 h at room temperature. Thereaction was then quenched by the addition of 5 mL of water/ice. Theresulting solution was extracted with 3×10 mL of ethyl acetate and theorganic layers combined. The resulting mixture was concentrated undervacuum affording the title compound (460 mg, 75%) as a colorless oil.MS: (ES, m/z): 232 [M+H]⁺.

Step 2. Synthesis of 2-(3-(benzyloxy)propyl)-5-methyloxazole

Into a 100-mL round-bottom flask, was placed4-(benzyloxy)-N-(prop-2-yn-1-yl)butanamide (460 mg, 1.99 mmol) inacetonitrile (10 mL). Goldtrichloride (30.05 mg, 0.1 mmol) was added andthe resulting solution was stirred for 8 h at 50° C. The resultingmixture was concentrated under vacuum and the residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (1:5).This afforded the title compound (280 mg, 61%) as a yellow oil. MS: (ES,m/z): 232 [M+H]⁺.

Step 3. Synthesis of 3-(5-methyloxazol-2-yl)propan-1-ol

Into a 50-mL round-bottom flask, was placed2-[3-(benzyloxy)propyl]-5-methyl-1,3-oxazole (280 mg, 1.21 mmol) and 10%palladium on carbon (28 g) in methanol (5 mL). A balloon filled withhydrogen (g) was charged in and the suspension was stirred for 12 h atroom temperature. The reaction was vented to nitrogen and the solidswere filtered out over celite. The resulting solution was concentratedunder vacuum affording the title compound (150 mg, 88%) as a whitesolid. MS: (ES, m/z): 142 [M+H]⁺.

Step 4. Synthesis of 3-(5-methyloxazol-2-yl)propanal

Into a 100-mL round-bottom flask, was placed3-(5-methyl-1,3-oxazol-2-yl)propan-1-ol (150 mg, 1.06 mmol) indichloromethane (5 mL). The reaction was cooled to 0° C. and Dess-Martinreagent (586.4 mg, 1.38 mmol) was added. The resulting mixture wasstirred for 1.5 h at room temperature and then concentrated undervacuum. This afforded the title compound (100 mg, 68%) as a white solid.MS: (ES, m/z): 140 [M+H]⁺.

Intermediate 21: 3-(3-methylisoxazol-5-yl)propanal

Step 1. Synthesis of 3-(3-methyl-1,2-oxazol-5-yl)propan-1-ol

Into a 100-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, 3,5-dimethyl-1,2-oxazole (2 g, 20.59 mmol) wasdissolved in tetrahydrofuran (20 mL). Then n-butyllithium (10 M inhexanes, 8.25 mL, 87.58 mmol) was added dropwise. The resulting mixturewas stirred at −78° C. for 2 h. To this was added a solution of oxirane(2.72 g, 61.8 mmol) in tetrahydrofuran (5 mL). The resulting solutionwas stirred at −78° C. for 1 h. The resulting solution was diluted with50 mL of ammonium chloride (aq.) and extracted with 3×50 mL ofdichloromethane. The organic layers were combined, dried over anhydroussodium sulfate, filtered and concentrated under vacuum. This affordedthe title compound (1.47 g, crude) as an orange liquid. MS: (ES, m/z):142 [M+H]⁺.

Step 2. Synthesis of 3-(3-methyl-1,2-oxazol-5-yl)propanal

Into a 25-mL round-bottom flask, 3-(3-methyl-1,2-oxazol-5-yl)propan-1-ol(500 mg, 3.54 mmol) was dissolved in dichloromethane (5 mL). ThenDess-Martin periodinane (1.95 g, 4.61 mmol) was added. The resultingsolution was stirred for 2 h at room temperature. The resulting solutionwas diluted with 50 mL of sodium bicarbonate and extracted with 3×50 mLof ethyl acetate. The organic layers were combined, dried over anhydroussodium sulfate, filtered and concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:1). This afforded the title compound (247 mg, 50%) as a lightyellow liquid. MS: (ES, m/z): 140 [M+H]⁺.

Intermediate 22: 3-(5-methyl-1,3,4-oxadiazol-2-yl)propanal

Step 1. Synthesis of N′-acetyl-4-(benzyloxy)butanehydrazide

Into a 250-mL 3-necked round-bottom flask purged and maintained with aninert atmosphere of nitrogen, was placed 4-(benzyloxy)butanoic acid (1.0g, 5.15 mmol) in dichloromethane (10 mL). Acetohydrazide (724 mg, 9.77mmol) was added followed by triethylamine (1.249 g, 12.34 mmol),4-dimethylaminopyridine (1.25 g, 10.23 mmol) and EDC (1.98 g, 10.31mmol). The resulting solution was stirred for 17 h at room temperature.The pH value of the solution was adjusted to 2 with hydrochloric acid(1N). The resulting solution was extracted with 2×20 mL of ethyl acetateand the organic layers combined. The resulting mixture was concentratedunder vacuum affording the title compound (1 g, 78%) as a white solid.MS: (ES, m/z): 251 [M+H]⁺.

Step 2. Synthesis of 2-(3-(benzyloxy)propyl)-5-methyl-1,3,4-oxadiazole

Into a 50-mL round-bottom flask, was placedN′-acetyl-4-(benzyloxy)butanehydrazide (300 mg, 1.20 mmol) inacetonitrile (5 mL). Phosphoroyl trichloride (5 mL) was added and theresulting solution was stirred for 2 h at 60° C. The resulting mixturewas concentrated under vacuum and the residue was subjected topurification by FCC eluting with ethyl acetate. This afforded the titlecompound (180 mg, 65%) as a yellow oil. MS: (ES, m/z): 233 [M+H]⁺.

Step 3. Synthesis of 3-(5-methyl-1,3,4-oxadiazol-2-yl)propan-1-ol

Into a 50-mL round-bottom flask, was placed a suspension of2-[3-(benzyloxy)propyl]-5-methyl-1,3,4-oxadiazole (180 mg, 0.77 mmol),and 10% palladium on carbon (18 mg) in methanol (5 mL). A balloon filledwith hydrogen (g) was charged in and the reaction mixture was stirredfor 24 h at room temperature. The reaction was vented to nitrogen andthe solids were filtered out over celilte. The filtered solution wasconcentrated in vacuo and the residue was subjected to purification byFCC eluting with ethyl acetate. This afforded the title compound (100mg, 91%) as a white solid. MS: (ES, m/z): 143 [M+H]⁺.

Step 4. Synthesis of 3-(5-methyl-1,3,4-oxadiazol-2-yl)propanal

Into a 100-mL 3-necked round-bottom flask, was placed3-(5-methyl-1,3,4-oxadiazol-2-yl)propan-1-ol (100 mg, 0.70 mmol) indichloromethane (5 mL). Dess-Martin periodinane reagent (388 mg, 0.91mmol) was added and the resulting solution was stirred for 1 h at roomtemperature. The resulting mixture was concentrated under vacuum. Theresidue was dissolved in 5 mL of ethyl acetate. The solids were filteredout over celite and the filtered solution was concentrated in vacuo. Theresidue was subjected to purification by FCC eluting with ethyl acetate.This afforded the title compound (80 mg, 81%) as a yellow oil. MS: (ES,m/z): 141 [M+H]⁺.

Intermediate 23: 3-(5-methyl-1,3,4-oxadiazol-2-yl)propanal

Step 1. Methyl (2E)-3-(1-methyl-1H-pyrazol-3-yl)prop-2-enoate

Into a 50-mL vial purged and maintained with an inert atmosphere ofnitrogen, 3-iodo-1-methyl-1H-pyrazole (500 mg, 2.40 mmol) was dissolvedin acetonitrile (10 mL). Then methyl prop-2-enoate (2.07 g, 24.03 mmol),palladium diacetate (108 mg, 0.48 mmol), tri-ortho-tolylphosphine (292mg, 0.96 mmol) and triethylamine (1.216 g, 12.02 mmol) were added. Theresulting solution was stirred for 2 h at 80° C. under nitrogenatmosphere. The reaction mixture was cooled and concentrated undervacuum. The residue was subjected to purification by FCC eluting withethyl acetate/petroleum ether (1:1). This afforded the title compound(130 mg, 33%) as a yellow oil. MS: (ES, m/z): 167[M+H]⁺.

Step 2. Methyl 3-(1-methyl-1H-pyrazol-3-yl)propanoate

Into a 50-mL round-bottom flask, methyl(2E)-3-(1-methyl-1H-pyrazol-3-yl)prop-2-enoate (130 mg, 0.78 mmol) wasdissolved in methanol (10 mL). Then 10% palladium on carbon (80 mg, 0.75mmo) was added. Hydrogen (g) was charged into the reaction mixture. Theresulting solution was stirred for 1 h at room temperature underhydrogen atmosphere. The reaction was vented to nitrogen and the solidswere filtered out and the resulting mixture was concentrated undervacuum. The residue was subjected to purification by FCC eluting withethyl acetate/petroleum ether (1:1). This afforded the title compound(120 mg, 91%) as an off-white oil. MS: (ES, m/z): 169 [M+H]⁺.

Step 3. 3-(1-Methyl-1H-pyrazol-3-yl)propan-1-ol

Into a 25-mL round-bottom flask, methyl3-(1-methyl-1H-pyrazol-3-yl)propanoate (150 mg, 0.89 mmol) was dissolvedin tetrahydrofuran (10 mL) Then lithium aluminium hydride (40 mg, 1.05mmol) was added. The resulting solution was stirred for 1 h at roomtemperature. The reaction was then quenched by addition of water (20mL). The resulting solution was extracted with 3×20 mL of ethyl acetate.The organic layers were combined, dried over sodium sulfate, filteredand concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (1:1). This affordedthe title compound (120 mg, 96%) as an off-white oil. MS: (ES, m/z): 141[M+H]⁺.

Step 4. 3-(1-methyl-1H-pyrazol-3-yl)propanal

Into a 50-mL round-bottom flask, 3-(1-methyl-1H-pyrazol-3-yl)propan-1-ol(120 mg, 0.86 mmol) was dissolved in dichloromethane (10 mL). ThenDess-Martin periodinane (472 mg, 1.11 mmol) was added in portions. Theresulting solution was stirred for 2 h at 0° C. in a water/ice bath. Thereaction was then quenched by addition of water (20 mL). The resultingsolution was extracted with 3×20 mL of dichloromethane. The organiclayers were combined, dried over sodium sulfate, filtered andconcentrated under vacuum. The residue was subjected to purification byFCC eluting with ethyl acetate/petroleum ether (1:1). This afforded thetitle compound (100 mg, 85%) as an off-white oil. MS: (ES, m/z):139[M+H]⁺.

Intermediate 24: 3-((tert-butyldimethylsilyl)oxy)-2-phenylpropanal

Step 1. Synthesis of3-[(tert-butyldimethylsilyl)oxy]-2-phenylpropan-1-ol

Into a 100-mL round-bottom flask, 2-phenylpropane-1,3-diol (2.5 g, 16.43mmol) was dissolved in dichloromethane (30 mL). Thentert-butyldimethylsilyl chloride (2.6 g, 17.25 mmol) and4-dimethylaminopyridine (20 mg, 0.16 mmol) were added, followed bytriethylamine (2.7 mL, 19.42 mmol). The mixture was stirred for 12 h atroom temperature. The resulting mixture was concentrated under vacuum.The residue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:5). This afforded the title compound (2 g,46%) as a yellow oil. MS: (ES, m/z): 267 [M+H]⁺.

Step 2. Synthesis of 3-[(tert-butyldimethylsilyl)oxy]-2-phenylpropanal

Into a 50-mL round-bottom flask,3-[(tert-butyldimethylsilyl)oxy]-2-phenylpropan-1-ol (1 g, 3.75 mmol)was dissolved in dichloromethane (20 mL) and cooled down to 0° C. ThenDess-Martin periodinane (2 g, 4.72 mmol) was added. The mixture wasstirred for 8 h at room temperature. Then water was added. The mixturewas extracted with 2×50 mL of dichloromethane. The organic layers werecombined, dried over sodium sulfate, filtered and concentrated. Theresidue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:4). This afforded the title compound (800 mg,81%) as a yellow oil. MS: (ES, m/z): 265 [M+H]⁺.

Intermediate 25 and 26: methyl(cis)-4-amino-2,2-dimethylcyclohexane-1-carboxylate and methyl(trans)-4-amino-2,2-dimethylcyclohexane-1-carboxylate

Step 1. Synthesis of cis-methyl4-(benzylamino)-2,2-dimethylcyclohexanecarboxylic acid and trans-methyl4-(benzylamino)-2,2-dimethylcyclohexanecarboxylic acid

Into a 100-mL round-bottom flask, methyl2,2-dimethyl-4-oxocyclohexane-1-carboxylate (1 g, 5.43 mmol) wasdissolved in methanol (20 mL). Then phenylmethanamine (1.61 g, 10.86mmol) was added. The resulting solution was stirred for 1 h at roomtemperature. Then sodium cyanoborohydride (1.37 g, 21.72 mmol) wasadded, followed by glacial acetic acid (980 mg, 16.33 mmol). Theresulting solution was stirred for 8 h at room temperature. The solidswere filtered out and the resulting mixture was concentrated undervacuum. The crude product was purified by Prep-HPLC with the followingconditions: Column, XBridge C18 OBD Prep Column, 5 um, 19 mm×150 mm;mobile phase, A: Water (containing 10 mmol/L NH₄HCO₃) and B: ACN (20.0%to 40.0% ACN over 7 min); UV Detector: 254 nm. This result in 890 mg(60%) of the product as a yellow oil. The product was then purified byChiral Prep-HPLC with the following conditions: Column: CHIRALPAK IF,2*25 cm, 5 um; Mobile Phase, A: hexanes and B: EtOH (30% EtOH over 11.5min); UV Detector: 254 nm; RT1:6.97 and RT2:7.25. This afforded thetitle compounds 380 mg of cis-methyl4-(benzylamino)-2,2-dimethylcyclohexanecarboxylic acid as a yellow oiland 200 mg of trans-methyl4-(benzylamino)-2,2-dimethylcyclohexanecarboxylic acid as a yellow oil.MS: (ES, m/z): 262 [M+H]⁺.

Step 2. Synthesis of methyl(cis)-4-amino-2,2-dimethylcyclohexane-1-carboxylate and methyl(trans)-4-amino-2,2-dimethylcyclohexane-1-carboxylate

Into a 100-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl4-(benzylamino)-2,2-dimethylcyclohexane-1-carboxylate (380 mg, 1.38mmol) was dissolved in methanol (14 mL). Then palladium on carbon (76mg, 10%) was added, followed by acetic acid (0.7 mL). Hydrogen (g) wascharged into the reaction mixture and the resulting solution was stirredunder a hydrogen atmosphere for 8 h at room temperature. The reactionwas vented to nitrogen and the solids were filtered out over celite. Thefiltered solution was concentrated under vacuum. This afforded the titlecompound (203 mg, crude) as a yellow oil, which could be used withoutfurther purification. MS: (ES, m/z): 186 [M+H]⁺.

Intermediate 27: 2-methyl-3-phenylpropanal

Step 1. Synthesis of 2-methyl-3-phenylpropan-1-ol

Into a 250-mL round-bottom flask, 2-methyl-3-phenylpropanoic acid (3.0g, 18.3 mmol) was dissolved in tetrahydrofuran (30 mL). Then borontrifluoride tetrahydrofuran complex (27 mL, 282.1 mmol) was addeddropwise with stirring at 0° C. The resulting solution was stirred for 2h at room temperature. The reaction was then quenched by addition of 30mL of water and extracted with 3×50 mL of ethyl acetate. The organiclayers were combined, dried over anhydrous sodium sulfate, filtered andconcentrated under vacuum. This afforded the title compound (2.0 g, 70%)as a yellow oil. MS: (ES, m/z): 151 [M+H]⁺.

Step 2. Synthesis of 2-methyl-3-phenylpropanal

Into a 250-mL round-bottom flask, 2-methyl-3-phenylpropan-1-ol (2.0 g,13.3 mmol) was dissolved in dichloromethane (50 mL). Then Dess-Martinperiodinane reagent (11.3 g, 26.6 mmol) was added. The resultingsolution was stirred for 5 h at room temperature. The reaction was thenquenched by addition of 100 mL of saturated sodium bicarbonate solutionand extracted with 3×50 mL of dichloromethane. The organic layers werecombined, dried over anhydrous sodium sulfate, filtered and concentratedunder vacuum. The residue was subjected to purification by FCC elutingwith ethyl acetate/petroleum ether (1:4). This afforded the titlecompound (1.0 g, 49%) as a yellow oil. MS: (ES, m/z): 149 [M+H]⁺.

Intermediate 28: 2-(3-isopropoxyphenyl)acetaldehyde

Step 1. Synthesis of propan-2-yl 2-[3-(propan-2-yloxy)phenyl]acetate

Into a 250-mL round-bottom flask, 2-(3-hydroxyphenyl)acetic acid (2 g,13.15 mmol) was dissolved in N,N-dimethylformamide (50 mL). Thenpotassium carbonate (5.45 g, 39.43 mmol) was added, followed by2-iodopropane (6.71 g, 39.47 mmol). The resulting solution was stirredfor 5 h at 60° C. The reaction mixture was cooled to room temperatureand diluted with 100 mL of water. The resulting solution was extractedwith 3×100 mL of ethyl acetate. The organic layers were combined, driedover anhydrous sodium sulfate, filtered and concentrated under vacuum.This afforded the title compound (1.7 g, crude) as a yellow oil. MS:(ES, m/z): 237 [M+H]⁺.

Step 2. Synthesis of 2-[3-(propan-2-yloxy)phenyl]ethan-1-ol

Into a 50-mL round-bottom flask, propan-2-yl2-[3-(propan-2-yloxy)phenyl]acetate (1.5 g, 4.44 mmol) was dissolved intetrahydrofuran (10 mL). Then lithium aluminum hydride (362 mg, 9.54mmol) was added in portions. The resulting solution was stirred for 2 hat room temperature. The reaction was then quenched by the addition of20 mL of potassium sodium tartrate (aq) and extracted with 3×30 mL ofethyl acetate. The organic layers were combined, dried over anhydroussodium sulfate, filtered and concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:1). This afforded the title compound (0.9 g, 75%) as a yellowoil. MS: (ES, m/z): 181 [M+H]⁺.

Step 3. Synthesis of 2-(3-isopropoxyphenyl)acetaldehyde

Into a 50-mL round-bottom flask, 2-[3-(propan-2-yloxy)phenyl]ethan-1-ol(150 mg, 0.83 mmol) was dissolved in chloroform (10 mL). ThenDess-Martin periodinane (530 mg, 1.25 mmol) was added. The resultingsolution was stirred for 2 h at room temperature. The solids werefiltered out and the filtrate was diluted with 30 mL of sodiumbicarbonate(aq). The resulting solution was extracted with 3×30 mL ofethyl acetate. The organic layers were combined, dried over anhydroussodium sulfate, filtered and concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:1). This afforded the title compound (75 mg, 48%) as a yellowoil. MS: (ES, m/z): 179 [M+H]⁺.

Intermediate 29: 3-aminocyclohexane-1-carbonitrile hydrochloride

Step 1. Synthesis of tert-butyl N-(3-cyanocyclohexyl)carbamate

Into a 50-mL round-bottom flask, tert-butylN-(3-carbamoylcyclohexyl)carbamate (2.0 g, 8.25 mmol) was dissolved indichloromethane (20 mL). Then trifluoroacetic anhydride (3.8 g, 18.09mmol) and triethylamine (1.8 g, 17.79 mmol) were added. The resultingsolution was stirred for 3 h at −10° C. in an ice/salt bath. Theresulting mixture was washed with 3×20 mL of water. The organic layerwas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (1:1). This affordedthe title compound (1.27 g, 69%) as a white solid. MS: (ES, m/z): 225[M+H]⁺.

Step 2. Synthesis of 3-aminocyclohexane-1-carbonitrile hydrochloride

Into a 50-mL round-bottom flask, tert-butyl N-3-cyanocyclohexylcarbamate (500 mg, 2.01 mmol) was dissolved in 1, 4-dioxane. Then 4 Nhydrochloric acid (2 mL) was added. The resulting solution was stirredfor 4 h at room temperature. The resulting mixture was concentratedunder vacuum. The residue was washed with 3×10 mL of petroleum ether.The solids were collected by filtration. This afforded the titlecompound (258 mg, 70%) as a white solid. MS: (ES, m/z): 125 [M+H]⁺.

Intermediate 30:(3R,6S)-6-(((tert-butyldimethylsilyl)oxy)methyl)tetrahydro-2H-pyran-3-amine

Step 1. Synthesis of[(2R,3S)-3-(acetyloxy)-3,6-dihydro-2H-pyran-2-yl]methyl acetate

Into a 2-L 3-necked round-bottom flask,[(2R,3S,4R)-3,4-bis(acetyloxy)-3,4-dihydro-2H-pyran-2-yl]methyl acetate(100 g, 367.31 mmol) was dissolved in dichloromethane (500 mL). Thentriethylsilane (43 g, 369.81 mmol) and BF₃-Et₂O (68 g, 479.12 mmol) wereadded. The resulting solution was stirred for 2 h at room temperature.The reaction was then quenched by the addition of 100 mL of sodiumbicarbonate. The mixture was washed with water (3×200 mL) and brine (200mL). The organic layers were combined, dried over anhydrous sodiumsulfate, filtered and concentrated. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (1:3).This afforded the title compound (72 g, 92%) as a yellow oil. MS: (ES,m/z): 215 [M+H]⁺.

Step 2. Synthesis of (2R,3S)-2-(hydroxymethyl)-3,6-dihydro-2H-pyran-3-ol

Into a 1-L round-bottom flask,[(2R,3S)-3-(acetyloxy)-3,6-dihydro-2H-pyran-2-yl]methyl acetate (36 g,168.06 mmol) was dissolved in methanol (200 mL). Then t-BuOK (1.3 g,11.59 mmol) was added. The resulting solution was stirred for 1 h atroom temperature. Then the mixture was neutralized by Dowex (H+ Form).The solids were filtered out. The resulting mixture was concentratedunder vacuum. The residue was subjected to purification by FCC elutingwith dichloromethane/methanol (10:1). This afforded the title compound(19 g, 87%) as a yellow oil. MS: (ES, m/z): 131 [M+H]⁺.

Step 3. Synthesis of(2R,3S)-2-[[(tert-butyldimethylsilyl)oxy]methyl]-3,6-dihydro-2H-pyran-3-ol

Into a 1000-mL 3-necked round-bottom flask,(2R,3S)-2-(hydroxymethyl)-3,6-dihydro-2H-pyran-3-ol (19 g, 145.99 mmol)was dissolved in pyridine (200 mL). Then TBSCI (21.9 g, 145.30 mmol) wasadded. The resulting solution was stirred for 12 h at room temperature.The resulting mixture was concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:10). This afforded the title compound (28.4 g, 80%) as a lightyellow oil. MS: (ES, m/z): 245 [M+H]⁺.

Step 4. Synthesis of(2R,3S)-2-(((tert-butyldimethylsilyl)oxy)methyl)-3,6-dihydro-2H-pyran-3-yl2,2,2-trichloroacetimidate

Into a 1000-mL 3-necked round-bottom flask,(2R,3S)-2-[[(tert-butyldimethylsilyl)oxy]methyl]-3,6-dihydro-2H-pyran-3-ol(33 g, 135.02 mmol) was dissolved in dichloromethane (500 mL). Then DBU(26.7 g, 175.38 mmol) and C₁₃CCN (25.2 g, 175.38 mmol) were added. Theresulting solution was stirred for 2 h at room temperature. Theresulting mixture was concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:10). This afforded the title compound (42 g, 80%) as a yellowoil. MS: (ES, m/z): 388, 390, 392 [M+H]⁺.

Step 5. Synthesis ofN-[(3R,6S)-6-[[(tert-butyldimethylsilyl)oxy]methyl]-3,6-dihydro-2H-pyran-3-yl]-2,2,2-trichloroacetamide

Into a 1-L round-bottom flask,(2R,3S)-2-(((tert-butyldimethylsilyl)oxy)methyl)-3,6-dihydro-2H-pyran-3-yl2,2,2-trichloroacetimidate (42 g, 108.03 mmol) was dissolved in1,2-dichlorobenzene (300 mL). Then potassium carbonate (1.5 g, 10.85mmol) was added. The resulting solution was stirred for 5 h at 180° C.The resulting mixture was cooled to room temperature and the solids werefiltered out. The resulting mixture was concentrated under vacuum. Theresidue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:5). This afforded the title compound (36 g,86%) as a white solid. MS: (ES, m/z): 388, 390, 392 [M+H]⁺.

Step 6. Synthesis of(3R,6S)-6-[[(tert-butyldimethylsilyl)oxy]methyl]-3,6-dihydro-2H-pyran-3-amine

Into a 100-mL round-bottom flask,N-[(3R,6S)-6-[[(tert-butyldimethylsilyl)oxy]methyl]-3,6-dihydro-2H-pyran-3-yl]-2,2,2-trichloroacetamide(2.0 g, 5.14 mmol) was dissolved in i-propanol (10 mL). Then potassiumhydroxide (868 mg, 15.47 mmol) was added. The resulting solution wasstirred for 12 h at room temperature. The solids were filtered out. Theresidue was subjected to purification by FCC eluting withdichloromethane/methanol (10:1). This afforded the title compound (1 g,80%) as a yellow oil. MS: (ES, m/z): 244 [M+H]⁺.

Step 7. Synthesis of(3R,6S)-6-(((tert-butyldimethylsilyl)oxy)methyl)tetrahydro-2H-pyran-3-amine

Into a 100-mL round-bottom flask,(3R,6S)-6-[[(tert-butyldimethylsilyl)oxy]methyl]-3,6-dihydro-2H-pyran-3-amine(1 g, 4.11 mmol) was dissolved in methanol (10 mL). Then palladium oncarbon (10%, 100 mg) was added. Hydrogen (g) was charged into thereaction mixture and the resulting mixture was stirred for 12 h at roomtemperature under hydrogen atmosphere. The reaction was vented tonitrogen and the solids were filtered out over celite. The filteredsolution was concentrated under a vacuum and the residue was subjectedto purification by FCC eluting with dichloromethane/methanol (10:1).This afforded the title compound (850 mg, 84%) as a yellow oil. MS: (ES,m/z): 246 [M+H]⁺.

Intermediate 31: 1-thia-6-azaspiro[3.3]heptane 1,1-dioxide hydrochloride

Step 1. Synthesis of tert-butyl3-(2-oxoethylidene)azetidine-1-carboxylate

Into a 250-mL round-bottom flask, tert-butyl3-oxoazetidine-1-carboxylate (11 g, 63.61 mmol) was dissolved indichloromethane (150 mL). Then2-(triphenyl-lambda5-phosphanylidene)acetaldehyde (24 g, 78.08 mmol) wasadded. The resulting solution was stirred for 6 h at 40° C. The reactionmixture was cooled to room temperature. The resulting mixture wasconcentrated under vacuum. The residue was subjected to purification byFCC eluting with ethyl acetate/petroleum ether (1:5). This afforded thetitle compound (11 g, 79%) as a yellow oil. MS: (ES, m/z): 198 [M+H]⁺.

Step 2. Synthesis oftert-butyl3-(acetylthio)-3-(2-oxoethyl)azetidine-1-carboxylate

Into a 250-mL round-bottom flask, tert-butyl3-(2-oxoethylidene)azetidine-1-carboxylate (11 g, 55.77 mmol) wasdissolved in tetrahydrofuran (100 mL). Then piperidine (0.39 mL, 3.90mmol) and ethanethioic S-acid (6 mL, 83.65 mmol) were added. Theresulting solution was stirred for 4 h at room temperature. Theresulting mixture was concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:2). This afforded the title compound (11 g, 63%) of as a yellowoil. MS: (ES, m/z): 274 [M+H]⁺.

Step 3. Synthesis of tert-butyl3-(2-hydroxyethyl)-3-sulfanylazetidine-1-carboxylate

Into a 500-mL 3-necked round-bottom flask, tert-butyl3-(acetylsulfanyl)-3-(2-oxoethyl)azetidine-1-carboxylate (18 g, 65.85mmol) was dissolved in ether (100 mL). Then LiAlH₄ (2.9 g, 76.41 mmol)was added. The resulting solution was stirred for 1 h at roomtemperature. The reaction was then quenched by the addition of 100 mL ofsodium bicarbonate (sat.). The resulting solution was extracted with3×100 mL of ethyl acetate. The organic layers were combined, dried overanhydrous sodium sulfate, filtered and concentrated. This afforded thetitle compound (9 g, 59%) as a brown oil. MS: (ES, m/z): 234 [M+H]⁺.

Step 4. Synthesis of tert-butyl1-thia-6-azaspiro[3.3]heptane-6-carboxylate

Into a 100-mL 3-necked round-bottom flask, tert-butyl3-(2-hydroxyethyl)-3-sulfanylazetidine-1-carboxylate (500 mg, 2.14 mmol)was dissolved in toluene (4 mL). Then diethyl triphenylphosphonite (1 g,2.84 mmol) was added. The resulting solution was stirred for 12 h atroom temperature. The resulting mixture was concentrated under vacuum.The residue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:5). This afforded the title compound (250 mg,49%) as a light yellow oil. MS: (ES, m/z): 216 [M+H]⁺.

Step 5. Synthesis of tert-butyl1-thia-6-azaspiro[3.3]heptane-6-carboxylate 1,1-dioxide

Into a 100-mL round-bottom flask, tert-butyl1-thia-6-azaspiro[3.3]heptane-6-carboxylate (250 mg, 1.16 mmol) wasdissolved in dichloromethane (10 mL). Then m-CPBA (400 mg, 2.32 mmol)was added. The resulting solution was stirred for 4 h at roomtemperature. The reaction was then quenched by the addition of 20 mL ofsodium bicarbonate (sat.). The resulting solution was extracted with3×100 mL of dichloromethane. Then the organic layers were combined,dried over anhydrous sodium sulfate, filtered and concentrated. Theresidue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:1). This afforded the title compound (200 mg,70%) as a white solid. MS: (ES, m/z): 248 [M+H]⁺.

Step 6. Synthesis of 1-thia-6-azaspiro[3.3]heptane 1,1-dioxidehydrochloride

Into a 50-mL round-bottom flask, tert-butyl1-thia-6-azaspiro[3.3]heptane-6-carboxylate 1,1-dioxide (50 mg, 0.20mmol) was dissolved in HCl (1 M in dioxane) (2 mL). The resultingsolution was stirred for 2 h at room temperature. The resulting mixturewas concentrated under vacuum. This afforded the title compound (20 mg,crude) as a white solid. MS: (ES, m/z): 148 [M+H]⁺.

Intermediate 32: methyl 4-oxo-2-phenylbutanoate

Step 1. Synthesis of methyl 4,4-diethoxy-2-phenylbutanoate

Into a 500-mL 3-necked round-bottom flask, methyl 2-phenylacetate (15 g,99.88 mmol) was dissolved in N,N-dimethylformamide (150 mL). Then KHMDS(527.56 mmol in 120 mL DMF) and 2-bromo-1,1-diethoxyethane (23.7 g,120.26 mmol) were added. The resulting solution was stirred for 30 minat 45° C. The resulting mixture was cooled to room temperature andquenched by the addition of 300 mL of NH₄Cl (aq.). The resultingsolution was extracted with 3×300 mL of ethyl acetate. The organiclayers were combined, dried over anhydrous sodium sulfate, filtered andconcentrated. The residue was subjected to purification by FCC elutingwith ethyl acetate/petroleum ether (1:10). This afforded the titlecompound (19.25 g, 72%) as a yellow oil. MS: (ES, m/z): 267 [M+H]⁺.

Step 2. Synthesis of methyl 4-oxo-2-phenylbutanoate

Into a 500-mL 3-necked round-bottom flask, methyl4,4-diethoxy-2-phenylbutanoate (19.25 g, 72.28 mmol) was dissolved inchloroform (20 mL). Then water (10 mL) and trifluoroacetic acid (96 mL,1.29 mol) were added. The resulting solution was stirred for 2 h at roomtemperature. The reaction was then quenched by the addition of 100 mL ofpotassium carbonate. The resulting solution was extracted with 3×100 mLof dichloromethane. The organic layers were combined, dried overanhydrous sodium sulfate, filtered and concentrated. This afforded thetitle compound (12.5 g, 90%) as a yellow oil. MS: (ES, m/z): 193 [M+H]⁺.

The following intermediates in TABLE B were prepared using standardchemical manipulations and procedures similar to those used for thepreparation of Intermediate 32.

TABLE B LRMS Intermediate m/z Number Structure and Compound Name [M +H]⁺ 33

211 34

211 35

226 36

226 37

228 38

207 39

207 40

241 41

225 42

240

Intermediate 43: tert-butyl((trans)-4-(methylsulfonyl)cyclohexyl)carbamate

Step 1. Synthesis of cis-4-((tert-butoxycarbonyl)amino)cyclohexylmethanesulfonate

A solution of cis-tert-butyl(4-hydroxycyclohexyl)carbamate (5.0 g, 23.22mmol) and triethylamine (6.47 ml, 46.4 mmol) in dichloromethane (50 ml)was cooled to 0° C. Mesyl chloride (2.71 ml, 34.8 mmol) was slowlyadded. The reaction mixture was allowed to stir at 0° C. for 20 minutes.The reaction was then quenched with water (20 mL). The layers wereallowed to separate and the organic layer was collected. The aqueouslayer was washed with additional dichloromethane (2×5 mL). The organiclayers were combined and washed with saturated ammonium chloride (10mL), saturated sodium bicarbonate (10 mL) and brine (10 mL). The organiclayer was then dried over sodium sulfate, filtered and concentrated toafford the title compound as a off-white solid. MS: (ES, m/z): 293[M+H]⁺.

Step 2. Synthesis of trans-4-((tert-butoxycarbonyl)amino)cyclohexyl)ethanethioate

thioacetic acid (2.57 ml, 35.8 mmol) was added to a stirred suspensionof potassium tert-butoxide (4.02 g, 35.8 mmol) in DMF (50 mL) at 0° C.The mixture was stirred for 5 mins and then a solution ofcis-4-((tert-butoxycarbonyl)amino)cyclohexyl methanesulfonate (7.0 g,23.86 mmol) in DMF (22.6 mL) was added. The mixture was heated to 80° C.for 4 hours and was then poured into a mixture of ethyl acetate (200 mL)and water (200 mL). The phases were separated and the aqueous phase wasextracted with ethyl acetate (×2). The combined organic extracts werewashed with 10% aqueous citric acid solution (200 mL), saturated sodiumhydrogen carbonate solution (200 mL), and brine (200 mL), dried oversodium sulfate, filtered and concentrated under vacuum. The crudeproduct was subjected to purification by FCC (Biotage SNAP 340 g;eluting with 10-30% EtOAc in hexanes) affording the title compound as alight orange solid. MS: (ES, m z): 273 [M+H]⁺.

Step 3. Synthesis of tert-butyl-trans-4-(methylthio)cyclohexyl)carbamate

A stirred solution of trans-4-((tert-butoxycarbonyl)amino)cyclohexyl)ethanethioate (2.0 g, 7.32 mmol) in MeOH (48 ml) was treated with sodiummethoxide (1.04 g, 19.25 mmol) followed by iodomethane (0.449 ml, 7.22mmol). The mixture was stirred at ambient temperature for 3 hours thendiluted with ethyl acetate (200 mL) and water (200 mL). The phases wereseparated and the aqueous phase was extracted with ethyl acetate (100mL×2). The combined organic extracts were washed with 10% aqueous citricacid solution (200 mL), saturated sodium hydrogen carbonate solution(200 mL), and brine (200 mL), dried over sodium sulphate, filtered andconcentrated under vacuum to give crude product. The crude product wassubjected to purification by FCC (Biotage SNAP 100 g; eluting with10-30% EtOAc in hexanes) affording the title compound as a white solid.MS: (ES, m/z): 246 [M+H]⁺.

Step 4. Synthesis of tert-butyl((trans)-4-(methylsulfonyl)cyclohexyl)carbamate

A solution of tert-butyl-trans-4-(methylthio)cyclohexyl)carbamate (1.0g, 4.08 mmol) in MeOH (14 ml) was cooled to 0° C. and treated with asuspension of oxone (2.505 g, 4.08 mmol) in water (6 ml). The mixturewas stirred at ambient temperature for 1 hour, then diluted with ethylacetate (100 mL) and water (100 mL). The phases were separated and theaqueous phase was extracted with ethyl acetate (100 mL×2). The combinedorganic extracts were washed with 10% aqueous citric acid solution (100mL), saturated sodium hydrogen carbonate solution (100 mL), and brine(100 mL), dried over sodium sulphate, filtered and concentrated undervacuum to afford the crude product. The crude product was subjected topurification by FCC (Biotage SNAP 100 g; eluting with 40-60% EtOAc inhexanes) affording the title compound as a white solid. MS: (ES, m/z):278 [M+H]⁺.

The disclosure is further illustrated by the following examples andsynthesis schemes, which are not to be construed as limiting thisdisclosure in scope or spirit to the specific procedures hereindescribed. It is to be understood that the examples are provided toillustrate certain embodiments and that no limitation to the scope ofthe disclosure is intended thereby. It is to be further understood thatresort may be had to various other embodiments, modifications, andequivalents thereof which may suggest themselves to those skilled in theart without departing from the spirit of the present disclosure and/orscope of the appended claims.

The synthetic schemes are presented for the synthesis of certaincompounds herein disclosed. The process and results for the assaystesting BET family bromodomain inhibition and effects on a cancer cellline proliferation are also described.

Examples 1 and 2: methyl(S)-3,7-dimethyl-2-((R)-2-phenylpropyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-3,7-dimethyl-2-((S)-2-phenylpropyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. methyl(2S)-6-bromo-2-methyl-5-(3-phenylbutanamido)-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 100-mL round-bottom flask, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(100 mg, 0.33 mmol, Intermediate 1) was dissolved in dichloromethane (8mL). Then pyridine (132 mg, 1.67 mmol) was added, followed by theaddition of a solution of 3-phenylbutanoyl chloride (73 mg, 0.40 mmol,Intermediate 2) in dichloromethane (2 mL) dropwise with stirring. Theresulting solution was stirred overnight at room temperature. Theresulting mixture was concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1/10-1/1). This afforded the title compound (50 mg, 34%) as awhite solid. MS: (ES, m/z): 445 [M+H]⁺.

Step 2. Methyl(2S)-6-amino-2-methyl-5-(3-phenylbutanamido)-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 8-mL vial, was placed a solution of methyl(2S)-6-bromo-2-methyl-5-(3-phenylbutanamido)-1,2,3,4-tetrahydroquinoline-1-carboxylate(50 mg, 0.11 mmol) in dimethylsulfoxide (2 mL). Next, cuprous iodide (20mg, 0.11 mmol), L-proline (30 mg, 0.26 mmol) and sodium hydroxide (25mg, 0.63 mmol) were added. The mixture was stirred for 1 minute beforeaddition of ammonium hydroxide (2 mL, 28%, 51.36 mmol). The resultingsolution was stirred for 2 h at 50° C. The resulting solution was cooledto room temperature and diluted with 20 mL of water. The resultingsolution was extracted with 3×20 mL of ethyl acetate. The organic layerswere combined, dried over anhydrous sodium sulfate, filtered andconcentrated under vacuum. This afforded the title compound (30 mg, 70%)as colorless oil. MS: (ES, m/z): 382 [M+H]⁺.

Step 3. methyl(7S)-7-methyl-2-(2-phenylpropyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask, methyl(2S)-6-amino-2-methyl-5-(3-phenylbutanamido)-1,2,3,4-tetrahydroquinoline-1-carboxylate(30 mg, 0.08 mmol) was dissolved in dimethylsulfoxide (2 mL). Next,acetic acid (2 mL) and 3 drops of sulfuric acid were added. Theresulting solution was stirred for 12 h at 60° C. The resulting solutionwas cooled to room temperature and diluted with 20 mL of water. Theresulting solution was extracted with 3×20 mL of ethyl acetate. Theorganic layers were combined, dried over anhydrous sodium sulfate,filtered and concentrated under vacuum. This afforded the title compound(25 mg, 87%) as colorless oil. MS: (ES, m/z): 364 [M+H]⁺.

Step 4. methyl(S)-3,7-dimethyl-2-((R)-2-phenylpropyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-3,7-dimethyl-2-((S)-2-phenylpropyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask, methyl(7S)-7-methyl-2-(2-phenylpropyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(45 mg, 0.12 mmol) was dissolved in tetrahydrofuran (5 mL). Then sodiumhydride (12 mg, 0.25 mmol, 60%) was added, followed by the addition ofiodomethane (35 mg, 0.25 mmol) dropwise with stirring. The resultingsolution was stirred for 2 h at room temperature. The reaction was thenquenched by the addition of 10 mL of water and concentrated. The crudeproduct was purified by Flash-Prep-HPLC with the following conditions(IntelFlash-1): Column, C18 silica gel; mobile phase: A: MeCN and B:water (containing 0.05% TFA) from 5% increasing to 40% within 30 min; UVDetector: 254 nm. The crude product was purified by Chiral-Prep-HPLCwith the following conditions: Column, CHIRAL ART Cellulose-SB, 250×20mm I.D.; mobile phase, A: hexanes and B: ethanol (hold 15.0% ethanol in15 min); UV Detector: 254 nm. This afforded the title compounds asfollows: 2.5 mg (5%) of methyl(7S)-3,7-dimethyl-2-[(2R)-2-phenylpropyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, first eluting isomer) as a yellow oil and 3.5mg (7%) of methyl(7S)-3,7-dimethyl-2-[(2S)-2-phenylpropyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, second eluting isomer) as a yellow oil Firsteluting isomer: ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.48-7.40 (m, 1H),7.27-7.13 (m, 5H), 7.01 (d, J=8.8 Hz, 1H), 4.81-4.77 (m, 1H), 3.78 (s,3H), 3.40-3.35 (m, 1H), 3.30-3.22 (m, 5H), 3.06-3.00 (m, 2H), 2.31-2.22(m. 1H), 1.76-1.68 (m, 1H), 1.44 (d, J=6.8 Hz, 3H), 1.17 (d, J=6.8 Hz,3H). MS: (ES, m/z): 378 [M+H]⁺.

Second eluting isomer: ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.48-7.40 (m,1H), 7.27-7.17 (m, 5H), 7.03 (d, J=8.8 Hz, 1H), 4.81-4.77 (m, 1H), 3.77(s, 3H), 3.41-3.38 (m, 1H), 3.32-2.99 (m, 7H), 2.30-2.21 (m. 1H),1.75-1.71 (m, 1H), 1.41 (d, J=6.8 Hz, 3H), 1.17 (d, J=6.4 Hz, 3H). MS:(ES, m/z): 378 [M+H]⁺.

The following examples in TABLE 1 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Examples 1 and 2.

TABLE 1 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 3 and 4

1^(st) eluting isomer = 378 2^(nd) eluting isomer = 378 1^(st) elutingisomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.43-7.41 (m, 1H), 7.22-7.19 (m,3H), 7.09-7.06 (m, 3H), 4.81-4.79 (m, 1H), 3.82 (s, 3H), 3.35-3.28 (m,6H), 3.08-3.01 (m, 2H), 2.31-2.28 (m, 1H), 1.75-1.45 (m, 4H), 1.17 (d, J= 6.6 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm):7.43-7.41 (m, 1H), 7.23-7.21 (m, 3H), 7.15-7.05 (m, 3H), 4.81-4.78 (m,1H), 3.79 (s, 3H), 3.44-3.29 (m, 6H), 3.08-3.03 (m, 2H), 2.31-2.28 (m,1H), 1.75-1.46 (m, 4H), 1.20 (d, J = 6.6 Hz, 3H) 5 and 6

1^(st) eluting isomer = 364 2^(nd) eluting isomer = 364 1^(st) elutingisomer ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.58-7.52 (m, 1H), 7.34-7.30 (m,3H), 7.25-7.23 (m, 2H), 7.10-7.05 (m, 1H), 4.82-4.76 (m, 1H), 4.56-4.51(m, 1H), 3.78 (s, 3H), 3.48 (s, 3H), 3.39-3.31 (m, 1H), 3.09-3.35 (m,1H), 2.31-2.22 (m, 1H), 1.91-1.89 (m, 3H), 1.77-1.72 (m, 1H), 1.25-1.16(m, 3H) 2^(nd) eluting isomer ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.45-7.40(m, 1H), 7.29-7.28 (m, 2H), 7.22-7.17 (m, 3H), 7.06 (d, J = 8.8 Hz, 1H),4.80-4.75 (m, 1H), 4.40-4.37 (m, 1H), 3.77 (s, 3H), 3.43- 4.31 (m, 4H),3.05-2.98 (m, 1H), 2.34-2.26 (m, 1H), 1.87- 1.85 (m, 3H), 1.72-1.67 (m,1H), 1.25-1.16 (m, 3H)

Example 7: methyl(S)-7-methyl-2-phenethyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis ofmethyl-(2S)-6-bromo-2-methyl-5-(3-phenylpropanamido)-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 50-mL round-bottom flask,methyl-(2S)-5,6-diamino-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(100 mg, 0.43 mmol, Intermediate 1) was dissolved in dichloromethane (10mL). Pyridine (1 mL) was added, followed by 3-phenylpropanoyl chloride(169 mg, 1.00 mmol). The resulting solution was stirred for 12 h at 40°C. The resulting mixture was concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:1). This afforded the title compound (100 mg, 55%) as a yellowsolid. MS: (ES, m/z): 431,433 [M+H]⁺.

Step 2. Synthesis ofmethyl-(2S)-6-amino-2-methyl-5-(3-phenylpropanamido)-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 8-mL sealed tube,methyl-(2S)-6-bromo-2-methyl-5-(3-phenylpropanamido)-1,2,3,4-tetrahydroquinoline-1-carboxylate(20 mg, 0.05 mmol) was dissolved in dimethyl sulfoxide (2 mL). Thenammonium hydroxide (1 mL, 28%, 25.68 mmol), copper iodide (4 mg, 0.02mmol), L-proline (3 mg, 0.03 mmol) and sodium hydroxide (12 mg, 0.3mmol) were added successively. The resulting solution was stirred for 12h at 40° C. The resulting solution was diluted with 20 mL of water andextracted with 3×20 mL of ethyl acetate. The organic layers werecombined, dried over anhydrous sodium sulfate, filtered and concentratedunder vacuum. The resulting mixture was concentrated under vacuum. Thisafforded the title compound (10 mg, crude) as colorless oil. MS: (ES,m/z): 368 [M+H]⁺.

Step 3. Synthesis ofmethyl-(7S)-7-methyl-2-(2-phenylethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 8-mL sealed tube,methyl-(2S)-6-amino-2-methyl-5-(3-phenylpropanamido)-1,2,3,4-tetrahydroquinoline-1-carboxylate(10 mg, 0.03 mmol) was dissolved in dimethyl sulfoxide (2 mL). Thenacetic acid (1 mL) and sulfuric acid (0.1 mL) were added. The resultingsolution was stirred for 12 h at 60° C. The resulting mixture was cooledto room temperature and diluted with water (10 mL). The resultingsolution was extracted with 3×20 mL of ethyl acetate.

The organic layers were combined, dried over anhydrous sodium sulfate,filtered and concentrated under vacuum. The crude product was purifiedwith the following conditions: Column: XBridge Prep C18 OBD Column, 5μm, 19×150 mm; Mobile Phase, A: water (containing 0.05% TFA) and B: ACN(5% B to 56% ACN over 7 min); UV Detector: 254 nm. This afforded thetitle compound (2.8 mg, 29%) as a brown oil. ¹H-NMR (CDCl₃, 400 MHz) δ(ppm): 7.70-7.68 (m, 1H), 7.38-7.31 (m, 1H), 7.29-7.20 (m, 1H),6.99-6.95 (m, 4H), 4.80-4.78 (m, 1H), 3.79 (s, 3H), 3.23 (br, 2H),2.99-2.68 (m, 4H), 2.12-2.04 (m, 1H), 1.82-1.72 (m, 1H), 1.08 (d, J=6.4Hz, 3H). MS: (ES, m/z): 350 [M+H]⁺.

The following examples in TABLE 2 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Example 7.

TABLE 2 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR  8

398 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.36 (d, J = 8.8 Hz, 1H), 7.30-7.29(m, 1H), 6.99-6.91 (m, 3H), 4.79-4.73 (m, 1H), 3.83 (s, 3H), 3.78 (s,3H), 3.17- 3.06 (m, 5H), 2.87-2.83 (m, 1H), 2.28- 2.21 (m, 1H),1.78-1.70 (m, 1H), 1.15- 1.13 (m, 3H)  9

336 ¹H-NMR: (CDCl₃, 400 MHz) δ (ppm): 7.40-7.26 (m, 7H), 4.81-4.77 (m,1H), 4.29 (s, 3.79 (s, 3H), 3.13-3.05 (m, 1H), 2.91-2.89 (m, 2.28-2.19(m, 1H), 1.75- 1.69 (m, 1H), 1.14 (d, J = 6.8 Hz, 3H) 10

364 ¹H-NMR: (CDCl₃, 300 MHz) δ (ppm): 7.48 (d, J = 9.0 Hz, 1H),7.33-7.19 (m, 5H), 7.08 (d, J = 9.0 Hz, 1H), 4.84- 4.78 (m, 1H), 3.81(s, 3H), 3.49 (s, 3H), 3.35-3.14 (m, 5H), 3.08-2.99 (m, 1H), 2.31-2.24(m, 1H), 1.79-1.63 (m, 1H), 1.16-1.13 (m, 3H) 11

354 ¹H-NMR: (CDCl₃, 400 MHz) δ (ppm): 7.84 (d, J = 9.2 Hz, 1H), 7.50 (s,1H), 7.29-7.26 (m, 1H), 7.20-7.17 (m, 1H), 6.15 (s, 1H), 4.84-4.77 (m,3H), 3.85- 3.72 (m, 5H), 3.49 (s, 3H), 3.19-3.05 (m, 2H), 2.22-2.13 (m,1H), 1.87-1.82 (m, 1H), 1.13 (d, J = 6.8 Hz, 3H) 12

351 ¹H-NMR: (CDCl₃, 300 MHz) δ (ppm): 8.63-8.62 (m, 1H), 7.70-7.67 (m,1H), 7.41-7.21 (m, 4H), 4.84-4.78 (m, 1H), 3.77 (s, 3H), 3.44-3.40 (m,2H), 3.33- 3.29 (m, 2H), 3.14-3.08 (m, 1H), 2.97- 2.88 (m, 1H),2.29-2.21 (m, 1H), 1.79- 1.70 (m, 1H), 1.40 (d, J = 6.9 Hz, 3H) 13

365 ¹H-NMR: (CDCl₃, 400 MHz) δ (ppm): 8.52-8.47 (m, 2H), 7.52-7.45 (m,2H), 7.21-7.18 (m, 1H), 7.08-7.06 (m, 1H), 4.81-4.76 (m, 1H), 3.78 (s,3H), 3.55 (s, 3H), 3.29-3.17 (m, 5H), 3.03-2.96 (m, 1H), 2.31-2.22 (m,1H), 1.75-1.61 (m, 1H), 1.15-1.12 (m, 3H) 14

365 ¹H-NMR: (CDCl₃, 400 MHz) δ (ppm): 8.72 (s, 2H), 7.93 (d, J = 9.2 Hz,1H), 7.804 (s, 2H), 7.30 (d, J = 9.2 Hz, 1H), 4.86-4.82 (m, 1H), 3.89(s,3H), 3.82 (s, 3H), 3.78-3.68 (m, 2H), 3.47 (s, 2H), 3.18-3.06 (m,2H), 2.24-2.17 (m, 1H), 1.88-1.85 (m, 1H), 1.14 (d, J = 6.4 Hz, 3H) 15

381 ¹H-NMR: (CDCl₃, 300 MHz) δ (ppm): 7.92 (d, J = 9.0 Hz, 1H),7.71-7.69 (m, 1H), 7.48-7.42 (m, 1H), 7.32 (d, J = 9.0 Hz, 1H), 6.63 (d,J = 9.0 Hz, 1H), 6.33-6.31 (m, 1H), 4.89-4.84 (m, 1H), 4.53-4.48 (m,2H), 4.08 (s, 3H), 3.84- 3.78 (m, 5H), 3.19-3.12 (m, 2H), 2.25- 2.18 (m,1H), 1.91-1.85 (m, 1H), 1.19- 1.15 (m, 3H)

Example 16:(1R,3R)-3-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid

Step 1. methyl(S)-5-amino-6-(((1R,3R)-3-(methoxycarbonyl)cyclohexyl)amino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 10-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl (1R,3R)-3-aminocyclohexane-1-carboxylatehydrochloride (130 mg, 0.67 mmol) was dissolved in dioxane (4 mL). Thenmethyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(100 mg, 0.33 mmol, Intermediate 1), Brettphos (72 mg, 0.13 mmol),3^(rd) Generation Brettphos precatalyst (61 mg, 0.07 mmol) and sodiumtert-butoxide (97 mg, 1.01 mmol) were added. The resulting solution wasstirred for 1 h at 100° C. under nitrogen atmosphere. The reactionmixture was cooled and the solids were filtered out. The resultingmixture was concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (2:1).This afforded the title compound (41.3 mg, 33%) as a dark green solid.MS: (ES, m/z): 376 [M+H]⁺.

Step 2. methyl(S)-2-benzyl-3-((1R,3R)-3-(methoxycarbonyl)cyclohexyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl methyl(S)-5-amino-6-(((1R,3R)-3-(methoxycarbonyl)cyclohexyl)amino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate(165.4 mg, 0.44 mmol) was dissolved in dichloromethane (5 mL). Then2-phenylacetaldehyde (158.8 mg, 1.32 mmol) was added. The resultingsolution was stirred for 2 h at room temperature. The resulting mixturewas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (2:1). This affordedthe title compound (122.9 mg, 59%) as a yellow solid. MS: (ES, m/z): 476[M+H]⁺.

Step 3.(1R,3R)-3-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid

Into a 25-mL round-bottom flask, methyl methyl(S)-2-benzyl-3-((1R,3R)-3-(methoxycarbonyl)cyclohexyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate(30 mg, 0.06 mmol) was dissolved in tetrahydrofuran (0.5 mL). Then water(0.5 mL) was added, followed by lithium hydroxide (7.0 mg, 0.29 mmol).The resulting solution was stirred for 3 h at 85° C. The pH value of thesolution was adjusted to 5-6 with hydrochloric acid (1 mol/L). Theresulting solution was extracted with ethyl acetate (3×20 mL). Theorganic layers were combined, dried over anhydrous sodium sulfate,filtered and concentrated under vacuum. The crude product was purifiedby Prep-HPLC with the following conditions: Column, XBridge C18 OBD PrepColumn, 100 Å, 5 μm, 19 mm×250 mm; mobile phase, A: Water (containing 10mmol/L NH₄HCO₃) and B: ACN (10.0% to 30.0% ACN over 10 min); UVDetector: 254 nm. This afforded the title compound (15.2 mg, 52%) as awhite solid.

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.47 (d, J=9.0 Hz, 1H), 7.39 (d, J=8.9Hz, 1H), 7.35-7.19 (m, 5H), 4.84-4.68 (m, 2H), 4.45-4.25 (m, 2H), 3.79(s, 3H), 3.22-3.14 (m, 1H), 2.98-2.85 (m, 2H), 2.40-2.02 (m, 5H),1.83-1.70 (m, 1H), 1.64-1.54 (m, 2H), 1.33-1.13 (m, 5H). MS: (ES, m z):462 [M+H]⁺.

The following examples in TABLE 3 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Example 16.

TABLE 3 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 17

462 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47 (d, J = 9.0 Hz, 1H), 7.39 (d,J = 8.9 Hz, 1H), 7.35-7.19 (m, 5H), 4.84- 4.68 (m, 2H), 4.45-4.25 (m,2H), 3.79 (s, 3H), 3.22-3.14 (m, 1H), 2.98-2.85 (m, 2H), 2.40-2.02 (m,5H), 1.83-1.70 (m, 1H), 1.64-1.54 (m, 2H), 1.33-1.13 (m, 5H) 18

462 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.51-7.20 (m, 7H), 4.82-4.74 (m,1H), 4.43 (s, 2H), 4.38-4.24 (m, 1H), 3.79 (s, 3H), 3.28-3.20 (m, 1H),3.02-2.94 (m, 1H), 2.37-1.95 (m, 5H), 1.94-1.67 (m, 3H), 1.50-1.28 (m,3H), 1.17 (d, J = 6.7 Hz, 3H) 19

462 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.51-7.20 (m, 7H), 4.82-4.74 (m,1H), 4.43 (s, 2H), 4.38-4.25 (m, 1H), 3.79 (s, 3H), 3.28-3.18 (m, 1H),3.02-2.92 (m, 1H), 2.38-1.95 (m, 5H), 1.93-1.70 (m, 3H), 1.50-1.28 (m,3H), 1.17 (d, J = 6.6 Hz, 3H) 20

434 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.51-7.20 (m, 7H), 4.82-4.74 (m,1H), 4.43 (s, 2H), 4.38-4.25 (m, 1H), 3.79 (s, 3H), 3.28-3.18 (m, 1H),3.02-2.92 (m, 1H), 2.38-1.95 (m, 5H), 1.93-1.70 (m, 3H), 1.50-1.28 (m,3H), 1.17 (d, J = 6.6 Hz, 3H) 21

434 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.89 (d, J = 9.0 Hz, 1H), 7.46 (d,J = 9.0 Hz, 1H), 7.39-7.12 (m, 5H), 4.98- 4.94 (m, 1H), 4.82-4.73 (m,1H), 4.42 (s, 2H), 3.80 (s, 3H), 3.31-2.79 (m, 5H), 2.52-2.19 (m, 3H),1.86-1.69 (m, 1H), 1.17 (d, J = 6.6 Hz, 3H) 22

462 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.34-7.22 (m, 7H), 4.77-4.73 (m,1H), 4.39 (s, 2H), 4.26-4.21 (m, 1H), 3.76 (s, 3H), 3.30-3.17 (m, 1H),2.97-2.93 (m, 1H), 2.60 (s, 1H), 2.43-2.16 (m, 5H), 1.78-1.72 (s, 1H),1.51-1.28 (m, 4H), 1.13 (d, J = 6.4 Hz, 3H) 23

462 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.49-7.22 (m, 7H), 4.78-4.72 (m,1H), 4.42 (s, 2H), 4.25-4.15 (m, 1H), 3.79 (s, 3H), 3.23-3.12 (m, 1H),2.98-2.91 (m, 1H), 2.37-3.07 (m, 4H), 2.04-1.96 (m, 2H), 1.78-1.70 (m,1H), 1.58-1.35 (m, 4H), 1.16 (d, J = 6.7 Hz, 3H) 24

474 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.62 (d, J = 9.2 Hz, 1H), 7.56-7.36(m, 1H), 7.42-7.16 (m, 3H), 7.07-6.98 (m, 2H), 4.82-4.78 (m, 1H), 4.58(s, 2H), 3.80 (s, 3H), 3.25-3.15 (m, 1H), 3.00- 2.90 (m, 1H), 2.70-2.48(m, 4H), 2.20- 2.10 (m, 1H), 2.09-1.98 (m, 2H), 1.92- 1.70 (m, 5H), 1.17(d, J = 6.7 Hz, 3H) 25

476 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.32-7.27 (m, 3H), 7.24-7.19 (m,4H), 4.74-4.71 (m, 1H), 4.36 (s, 2H), 4.30- 4.15 (m, 1H), 3.73 (s, 3H),3.23-3.08 (m, 1H), 3.01-2.84 (m, 1H), 2.36-2.08 (m, 5H), 1.81-1.64 (m,1H), 1.39-1.28 (m, 2H), 1.16-1.05 (m, 8H) 26

476 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.37-7.30 (m, 2H), 7.28-7.17 (m,5H), 4.77-4.71 (m, 1H), 4.37 (s, 2H), 4.20- 4.16 (m, 1H), 3.74 (s, 3H),3.19-3.14 (m, 1H), 2.99-2.91 (m, 1H), 2.31-2.18 (m, 3H), 1.76-1.62 (m,5H), 1.41-1.20 (m, 5H), 1.12 (d, J = 6.9 Hz, 3H) 27

492 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.42-7.35 (m, 2H), 7.18 (d, J = 8.7Hz, 2H), 6.89 (d, J = 8.7 Hz, 2H), 4.79- 4.75 (m, 1H), 4.32-4.21 (m,3H), 3.76- 3.75 (m, 6H), 3.24-3.21 (m, 1H), 3.00- 2.92 (m, 1H),2.38-2.02 (m, 6H), 1.78- 1.71 (m, 1H), 1.55-1.37 (m, 4H), 1.14 (d, J =6.9 Hz, 3H) 28

510 ¹H-NMR (DMSO-d6, 400 MHz) δ (ppm): 7.46 (s, 1H), 7.27 (d, J = 6.9Hz, 1H), 7.14-7.11 (m, 2H), 7.08-7.02 (m, 1H), 4.67-4.62 (m, 1H), 4.28(s, 3H), 3.78 (s, 3H), 3.66 (s, 3H), 3.10- 3.02 (m, 1H), 2.87-2.81 (m,1H), 2.36-2.33 (m, 1H), 2.15-2.08 (m, 3H), 1.95-1.91 (m, 2H), 1.67-1.62(m, 1H), 1.49-1.37 (m, 4H), 1.07 (d, J = 6.8 Hz, 3H) 29

476 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.83-7.82 (m, 2H), 7.34-7.26 (m,3H), 7.22-7.19 (m, 2H), 4.86-4.85 (m, 1H), 4.43-4.36 (m, 1H), 3.82 (s,3H), 3.66- 3.61 (m, 2H), 3.25-3.21 (m, 2H), 3.06- 2.99 (m, 2H),2.57-2.54 (m, 1H), 2.30- 2.13 (m, 5H), 1.96-1.91 (m, 1H), 1.63- 1.56 (m,4H), 1.16 (d, J = 6.9 Hz, 3H) 30

476 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.32-7.27 (m, 3H), 7.24-7.19 (m,4H), 4.74-4.71 (m, 1H), 4.36 (s, 2H), 4.30- 4.15 (m, 1H), 3.73 (s, 3H),3.23-3.08 (m, 1H), 3.01-2.84 (m, 1H), 2.36-2.08 (m, 5H), 1.81-1.64 (m,1H), 1.39-1.28 (m, 2H), 1.16-1.05 (m, 8H) 31

466 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.55-7.46 (m, 3H), 7.40-7.37 (d, J= 9 Hz, 1H), 6.24 (s, 1H), 4.80-4.71 (m, 1H), 4.69-4.64 (m, 2H),4.24-4.15 (m, 1H), 3.78 (s, 3H), 3.55-3.51 (m, 2H), 3.19-3.13 (m, 1H),2.99-2.89 (m, 1H), 2.51-2.44 (m, 1H), 2.29-2.13 (s, 5H), 1.80-1.60 (m,5H), 1.15-1.13 (d, J = 6.6 Hz, 3H) 32

467 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.83-7.81 (m, 1H), 7.63-7.62 (m,2H), 7.43-7.37 (m, 1H), 5.11-5.08 (m, 2H), 4.84-4.82 (m, 1H), 4.18-3.99(m, 3H), 3.81 (s, 3H), 3.15-3.13 (m, 2H), 2.48- 2.43 (m, 1H), 2.21-2.18(m, 5H), 1.90-1.86 (m, 1H), 1.71-1.59 (m, 4H), 1.16 (d, J = 5.1 Hz, 3H)33

481 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51 (d, J = 9.0 Hz, 1H), 7.39 (d,J = 8.9 Hz, 1H), 6.72 (s, 1H), 4.77-4.72 (m, 1H), 4.32-4.23 (m, 1H),3.78 (s, 3H), 3.33-3.30 (m, 2H), 3.23-3.09 (m, 3H), 2.92-2.84 (m, 1H),2.51-2.16 (m, 9H), 1.88-1.82 (m, 2H), 1.72-1.62 (m, 3H), 1.14 (d, J =6.6 Hz, 3H) 34

480 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.50-7.47 (d, J = 9.0 Hz, 1H),7.42- 7.36 (m, 2H), 7.27 (s, 1H), 4.80-4.74 (m, 1H), 4.29-4.21 (m, 1H),3.79 (s, 3H), 3.76 (s, 3H), 3.21-3.18 (m, 3H), 2.99-2.96 (m, 3H),2.48-2.16 (m, 6H), 1.68-1.66 (m, 5H), 1.13-1.11 (d, J = 6.6 Hz, 3H) 35

481 ¹H-NMR (DMSO-d6, 400 MHz) δ (ppm): 7.52-7.49 (d, J = 9.2 Hz, 1H),7.27-7.25 (d, J = 9.2 Hz, 1H), 6.70 (s, 1H), 4.65-4.61 (m, 1H), 4.34 (s,1H), 3.66 (s, 3H), 3.37-3.17 (m, 4H), 3.05- 3.01 (m, 1H), 2.81-2.74 (m,1H), 2.51-2.44 (m, 1H), 2.27-2.22 (m, 5H), 2.13-2.06 (m, 3H), 1.86-1.80(m, 2H), 1.65-1.57 (m, 3H), 1.05-1.04 (d, J = 6.4 Hz, 3H) 36

481 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.47-7.33 (m, 2H), 6.05 (s, 1H),4.77- 4.65 (m, 1H), 4.26 (t, J = 12.5 Hz, 1H), 3.73 (s, 3H), 3.39-3.31(m, 2H), 3.28-3.22 (m, 2H), 3.20-3.02 (m, 1H), 2.94-2.78 (m, 1H),2.53-2.22 (m, 3H), 2.22-2.06 (m, 6H), 1.88-1.76 (m, 2H), 1.76-1.55 (m,3H), 1.09 (d, J = 6.6 Hz, 3H) 37

481 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49-7.47 (m, 1H), 7.40 (d, J = 9.2Hz, 1H), 6.10 (s, 1H), 4.78-4.70 (m, 1H), 4.36-1.25 (m, 1H), 3.79 (s,3H), 3.43- 3.34 (m, 2H), 3.25-3.21 (m, 2H), 3.23-3.10 (m, 1H), 2.91-2.83(m, 1H), 2.50-2.40 (m, 1H), 2.39-2.15 (m, 8H), 1.88-1.58 (m, 5H), 1.14(d, J = 6.8 Hz, 3H) 38

482 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.51 (d, J = 9.0 Hz, 1H), 7.38 (d,J = 9.0 Hz, 1H), 4.76-4.70 (m, 1H), 4.41 (s, 1H), 3.76 (s, 3H),3.50-3.36 (m, 4H), 3.11-3.06 (m, 1H), 2.90-2.83 (m, 1H), 2.49 (s, 3H),2.43-2.18 (m, 6H), 2.00-1.97 (m, 2H), 1.78-1.66 (m, 3H), 1.12 (d, J =6.9 Hz, 3H) 39

480 ¹H-NMR (DMSO-d6, 400 MHz) δ (ppm): 7.54 (s, 1H), 7.51 (d, J = 9.2Hz, 1H), 7.27-7.24 (m, 2H), 4.66-4.62 (m, 1H), 4.53-4.49 (m, 2H), 4.19(s, 1H), 3.66 (s, 3H), 3.43-3.40 (m, 2H), 3.09-3.01 (m, 1H), 2.84-2.80(m, 1H), 2.50-2.44 (m, 1H), 2.22-2.11 (m, 3H), 2.10-1.98 (m, 5H),1.75-1.57 (m, 5H), 1.06 (d, J = 6.8 Hz, 3H) 40

480 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47-7.35 (m, 3H), 5.97 (s, 1H),4.77- 4.73 (m, 1H), 4.61-4.53 (m, 2H), 4.10-4.09 (m, 1H), 3.76 (s, 3H),3.48- 3.45 (m, 2H), 3.20-3.12 (m, 1H), 2.96-2.89 (m, 1H), 2.42-2.39 (m,1H), 2.26-2.10 (m, 5H), 2.01 (s, 3H), 1.75- 1.59 (m, 5H), 1.12 (d, J =6.8 Hz, 3H) 41

500 ¹H-NMR (DMSO-d6, 300 MHz) δ (ppm): 8.08 (s, 1H), 7.56-7.50 (m, 2H),7.29-7.26 (d, J = 9.0 Hz, 1H), 4.66-4.57 (m, 3H), 4.28-4.20 (m, 1H),3.67 (s, 3H), 3.18 (s, 1H), 3.05-3.02 (m, 2H), 2.86-2.78 (m, 1H),2.46-2.41 (m, 1H), 2.22-2.01 (m, 5H), 1.75-1.57 (m, 5H), 1.07-1.05 (d, J= 6.6 Hz, 3H) 42

482 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.47 (d, J = 9.0 Hz, 1H), 7.34 (d,J = 8.9 Hz, 1H), 4.78-4.61 (m, 1H), 4.46- 4.31 (m, 1H), 3.73 (s, 3H),3.52-3.37 (m, 4H), 3.18-3.03 (m, 1H), 2.91-2.75 (m, 1H), 2.47-2.31 (m,3H), 2.29 (s, 3H), 2.24-2.06 (m, 3H), 1.99-1.87 (m, 2H), 1.79-1.58 (m,3H), 1.08 (d, J = 6.6 Hz, 3H) 43

456 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.14-8.11 (m, 2H), 7.41-7.39 (m,1H), 7.33-7.30 (m, 2H), 7.16-7.13 (m, 3H), 6.95-6.89 (m, 3H), 4.71-4.79(m, 1H), 4.27 (s, 2H), 3.75 (s, 3H), 3.31-3.29 (m, 1H), 3.08-2.94 (m,1H), 2.36-2.24 (m, 1H), 1.82-1.74 (m, 1H), 1.17 (d, J = 6.6 Hz, 3H) 44

456 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.21-8.12 (m, 1H), 7.88-7.81 (m,1H), 7.64-7.55 (t, J = 7.8 Hz, 1H), 7.48- 7.37 (m, 2H), 7.23-7.07 (m,3H), 6.99- 6.85 (m, 3H), 4.85-4.76 (m, 1H), 4.28 (s, 2H), 3.78 (s, 3H),3.31-3.22 (m, 1H), 3.07-2.95 (m, 1H), 2.36-2.24 (m, 1H), 1.82-1.74 (m,1H), 1.17 (d, J = 6.6 Hz, 3H) 45

480 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.51-7.48 (m, 2H), 7.43-7.37 (m,1H), 6.10-6.09 (m, 1H), 4.77-4.75 (m, 1H), 4.35-4.30 (m, 1H), 3.84 (s,3H), 3.78 (s, 3H), 3.17-3.07 (m, 5H), 2.95-2.89 (m, 1H), 2.50-2.17 (m,6H), 1.79-1.70 (m, 5H), 1.16 (d, J = 6.9 Hz, 3H)

Examples 46 and 47: methyl(7S)-2-[(1R)-2-hydroxy-1-phenylethyl]-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(7S)-2-[(1S)-2-hydroxy-1-phenylethyl]-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(2S)-5-amino-2-methyl-6-[(oxan-4-yl)amino]-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 50-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(300 mg, 1.00 mmol, Intermediate 1) was dissolved in toluene (20 mL).Then oxan-4-amine (305 mg, 3.02 mmol), Brettphos (215 mg, 0.40 mmol),BrettPhos Pd G3 (182 mg, 0.20 mmol) and sodium tert-butoxide (289 mg,3.01 mmol) were added. The resulting solution was stirred for 1 h at110° C. in the nitrogen atmosphere. The reaction mixture was cooled andthe resulting solids were filtered out. The filtrate was concentratedunder vacuum. The residue was subjected to purification by FCC elutingwith ethyl acetate/petroleum ether (1:1). This afforded the titlecompound (200 mg, 62%) as a yellow oil. MS: (ES, m/z): 320 [M+H]⁺.

Step 2. Synthesis of methyl(7S)-2-[2-[(tert-butyldimethylsilyl)oxy]-1-phenylethyl]-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask, methyl(2S)-5-amino-2-methyl-6-[(oxan-4-yl)amino]-1,2,3,4-tetrahydroquinoline-1-carboxylate(150 mg, 0.47 mmol) was dissolved in dichloromethane (10 mL) Then3-[(tert-butyldimethylsilyl)oxy]-2-phenylpropanal (300 mg, 1.13 mmol,Intermediate 24) was added. The mixture was stirred for 2 h at roomtemperature. The resulting mixture was concentrated under vacuum. Theresidue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:1). This afforded the title compound (150 mg,57%) as a green oil. MS: (ES, m/z): 564 [M+H]⁺.

Step 3. Synthesis of methyl(7S)-2-[(1R)-2-hydroxy-1-phenylethyl]-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(7S)-2-[(1S)-2-hydroxy-1-phenylethyl]-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(7S)-2-[2-[(tert-butyldimethylsilyl)oxy]-1-phenylethyl]-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(150 mg, 0.27 mmol) was dissolved in tetrahydrofuran (5 mL). Thentetrabutylammonium fluoride (1 mL, 1M in THF) was added. The resultingsolution was stirred for 30 min at 0° C. Then the resulting solution wasallowed to react for 3 h at room temperature. The resulting solids werefiltered out. The filtrate was concentrated under vacuum. The crudeproduct was purified by Prep-HPLC with the following conditions: Column,XBridge C18 OBD Prep Column, 100 Å, 5 um, 19 mm×150 mm; mobile phase, A:Water (containing 10 mmol/L FA) and B: ACN (10.0% to 40.0% ACN over 7min); UV Detector: 254 nm. This afforded the title compounds as follows:2.9 mg (2%) of methyl(7S)-2-[(1R)-2-hydroxy-1-phenylethyl]-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, first eluting isomer, RT=5.2 min) as a whitesolid and 2.8 mg (2%) of methyl(7S)-2-[(1S)-2-hydroxy-1-phenylethyl]-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, second eluting isomer, RT=6.1 min) as a whitesolid.

First eluting isomer (46): ¹H-NMR (300 MHz, Methanol-d₄) δ 7.49-7.21 (m,7H), 4.82-4.70 (m, 1H), 4.68-4.58 (m, 1H), 4.58-4.42 (m, 2H), 4.23-4.14(m, 1H), 4.14-4.04 (m, 1H), 3.90-3.81 (m, 1H), 3.79 (s, 3H), 3.60-3.48(m, 1H), 3.31-3.25 (m, 1H), 3.22-3.07 (m, 1H), 3.07-2.97 (m, 1H),2.64-2.46 (m, 1H), 2.40-2.16 (m, 2H), 1.88-1.65 (m, 2H), 1.17 (d, J=6.6Hz, 3H), 0.82-0.70 (m, 1H). MS: (ES, m/z): 450 [M+H]⁺.

Second eluting isomer (47): ¹H-NMR (300 MHz, Methanol-d₄) δ 7.46-7.23(m, 7H), 4.83-4.72 (m, 1H), 4.67-4.58 (m, 1H), 4.57-4.41 (m, 2H),4.24-4.14 (m, 1H), 4.14-4.05 (m, 1H), 3.88-3.76 (m, 4H), 3.60-3.47 (m,1H), 3.42-3.36 (m, 1H), 3.22-3.07 (m, 1H), 3.07-2.92 (m, 1H), 2.68-2.51(m, 1H), 2.38-2.15 (m, 2H), 1.88-1.68 (m, 2H), 1.19 (d, J=6.6 Hz, 3H),0.77-0.67 (m, 1H). MS: (ES, m/z): 450 [M+H]⁺.

Examples 48 and 49:(1R,4S)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid and(1S,4R)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid

Step 1. Synthesis of methyl(S)-5-amino-6-(((1S,4R)-4-(methoxycarbonyl)-3,3-dimethylcyclohexyl)amino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 100-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(272 mg, 0.91 mmol, Intermediate 1) was dissolved in toluene (20 mL).Then cis-methyl 4-amino-2,2-dimethylcyclohexane-1-carboxylate (203 mg,1.09 mmol, Intermediate 25), BrettPhos Pd G3 (96 mg, 0.11 mmol),Brettphos (112 mg, 0.21 mmol) and sodium tert-butoxide (331 mg, 3.64mmol) were added. The resulting solution was stirred for 1 h at 100° C.under a nitrogen atmosphere. The reaction mixture was cooled and thesolids were filtered out. The filtrate was concentrated under vacuum.The residue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:1). This afforded the title compound (60 mg,16%) as a yellow oil. MS: (ES, m/z): 404 [M+H]⁺.

Step 2. Synthesis of methyl(S)-2-benzyl-3-((1S,4R)-4-(methoxycarbonyl)-3,3-dimethylcyclohexyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, (S)-methyl5-amino-6-(cis-4-(methoxycarbonyl)-3,3-dimethylcyclohexylamino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate(26 mg, 0.06 mmol) was dissolved in dichloromethane (4 mL). Then2-phenylacetaldehyde (60 mg, 0.50 mmol) was added. The resultingsolution was stirred for 2 h at room temperature. The reaction mixturewas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (1:1). This affordedthe title compound (21 mg, 65%) as a yellow oil. MS: (ES, m/z): 504[M+H]⁺.

Step 3. Synthesis of(1R,4S)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid and(1S,4R)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid

Into a 10-mL round-bottom flask, (S)-methyl3-(cis-4-(methoxycarbonyl)-3,3-dimethylcyclohexyl)-7-methyl-2-phenyl-8,9-dihydro-3H-imidazo[4,5-f]quinoline-6(7H)-carboxylate(21 mg, 0.042 mmol) was dissolved in tetrahydrofuran (3 mL). Water (1mL) was added, followed by lithium hydroxide (10 mg, 0.42 mmol). Theresulting solution was stirred for 8 h at 85° C. The reaction mixturewas cooled and concentrated under vacuum. The crude product was purifiedby Prep-HPLC with the following conditions: Column, XBridge C18 OBD PrepColumn, 100 Å, 5 um, 19 mm×250 mm; mobile phase, A: Water (containing 10mmol/L FA) and B: ACN (10.0% to 40.0% ACN over 19 min); UV Detector: 254nm. This afforded the title compounds as follows: 1.2 mg (5.8%) of(1R,4S)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid (assumed stereochemistry, first eluting isomer, RT=15.35 min) as awhite solid and 4.8 mg (24%) of(1S,4R)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid (assumed stereochemistry, second eluting isomer, RT=17.15 min) as awhite solid.

First eluting isomer: ¹H-NMR (400 MHz, CDCl₃,ppm) δ 7.79 (d, J=9.2 Hz,1H), 7.44-7.30 (m, 4H), 7.24-7.17 (m, 2H), 4.94-4.79 (m, 1H), 4.79-4.56(m, 2H), 4.56-4.41 (m, 1H), 3.82 (s, 3H), 3.33-3.31 (m, 2H), 2.37-2.26(m, 1H), 2.26-1.99 (m, 3H), 1.96-1.81 (m, 2H), 1.81-1.60 (m, 2H),1.37-1.24 (m, 1H), 1.16 (d, J=6.4 Hz, 3H), 1.06 (s, 3H), 0.81 (s, 3H).MS: (ES, m/z): 490 [M+H]⁺.

Second eluting isomer: ¹H-NMR (400 MHz, CDCl₃, ppm) δ 7.81 (d, J=8.8 Hz,1H), 7.40-7.29 (m, 4H), 7.25-7.19 (m, 2H), 4.91-4.75 (m, 1H), 4.68 (s,2H), 4.57-4.39 (m, 1H), 3.82 (s, 3H), 3.30-3.00 (m, 2H), 2.36-2.25 (m,1H), 2.25-2.13 (m, 1H), 2.13-1.98 (m, 2H), 1.94-1.78 (m, 2H), 1.78-1.52(m, 2H), 1.45-1.33 (m, 1H), 1.15 (d, J=6.4 Hz, 3H), 1.08 (s, 3H), 0.84(s, 3H). MS: (ES, m/z): 490 [M+H]⁺.

Examples 50 and 51:(1R,4R)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid and(1S,4S)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid

Step 1. Synthesis of methyl(2S)-5-amino-6-[[trans-4-(methoxycarbonyl)-3,3-dimethylcyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 10-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(84 mg, 0.27 mmol, Intermediate 1) was dissolved in toluene (5 mL). Thentrans-methyl 4-amino-2,2-dimethylcyclohexane-1-carboxylate (156 mg, 0.84mmol, Intermediate 26), BrettPhos Pd G3 (51 mg, 0.06 mmol,), Brettphos(67 mg, 0.13 mmol), tert-butoxide (105 mg, 1.10 mmol). The resultingsolution was stirred for 1 h at 100° C. in the nitrogen atmosphere. Thereaction mixture was cooled and the solids were filtered out. Thefiltrate was concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (1:1).This afforded the title compound (55 mg, 48%) as a green oil. MS: (ES,m/z): 404 [M+H]⁺.

Step 2. Synthesis of(7S)-2-benzyl-3-[4-(methoxycarbonyl)-3,3-dimethylcyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 10-mL round-bottom flask, methyl(2S)-5-amino-6-[[trans-4-(methoxycarbonyl)-3,3-dimethylcyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(55 mg, 0.14 mmol) was dissolved in dichloromethane (5 mL). Then2-phenylacetaldehyde (50 mg, 0.41 mmol) was added. The resultingsolution was stirred for 2 h at room temperature. The reaction mixturewas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (1:1). This affordedthe title compound (20 mg, 29%) as a yellow oil. MS: (ES, m/z): 504[M+H]⁺.

Step 3. Synthesis of(1R,4R)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid and(1S,4S)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid

Into a 25-mL round-bottom flask, methyl(7S)-2-benzyl-3-[4-(methoxycarbonyl)-3,3-dimethylcyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(10 mg, 0.02 mmol) was dissolved in tetrahydrofuran (2 mL) then water (1mL) was added, followed by lithium hydroxide (4.6 mg, 0.19 mmol). Theresulting solution was stirred for 2 h at 85° C. The reaction mixturewas cooled and concentrated under vacuum. The crude product was purifiedby Prep-HPLC with the following conditions: Column, XBridge C18 OBD PrepColumn, 100 Å, 5 um, 19 mm×250 mm; mobile phase, A: Water (containing 10mmol/L FA) and B: ACN (10.0% to 40.0% ACN over 19 min); UV Detector: 254nm. This afforded the title compounds as follows: 2 mg (21%) of(1R,4R)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid (assumed stereochemistry, first eluting isomer, RT=14.7 min) as awhite solid and 2 mg (21%) of(1S,4S)-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-2,2-dimethylcyclohexane-1-carboxylicacid (assumed stereochemistry, second eluting isomer, RT=15.6 min) as awhite solid.

First eluting isomer: ¹H NMR (400 MHz, CDCl₃, ppm) δ 7.65 (d, J=9.2 Hz,1H), 7.43-7.33 (m, 1H), 7.31-7.27 (m, 1H), 7.24-7.15 (m, 4H), 4.86-4.75(m, 1H), 4.52 (d, J=16.4 Hz, 1H), 4.39-4.21 (m, 2H), 3.78 (s, 3H),3.32-3.18 (m, 1H), 3.11-3.00 (m, 1H), 2.80-2.67 (m, 1H), 2.67-2.52 (m,1H), 2.35-2.29 (m, 1H), 2.29-2.19 (m, 1H), 1.93-1.83 (m, 1H), 1.83-1.68(m, 2H), 1.44-1.35 (m, 1H), 1.16 (d, J=6.8 Hz, 3H), 0.99-0.92 (m, 4H),0.75 (s, 3H). MS: (ES, m/z): 490 [M+H]⁺.

Second eluting isomer: ¹H NMR (400 MHz, CDCl₃, ppm) δ 7.64 (d, J=8.0 Hz,1H), 7.43 (s, 1H), 7.32-7.27 (m, 1H), 7.24-7.15 (m, 4H), 4.85-4.73 (m,1H), 4.51-4.32 (m, 2H), 4.31-4.22 (m, 1H), 3.79 (s, 3H), 3.33-3.20 (m,1H), 3.15-3.00 (m, 1H), 2.78-2.65 (m, 1H), 2.55-2.38 (m, 1H), 2.33-2.17(m, 2H), 1.83-1.60 (m, 3H), 1.16 (d, J=6.8 Hz, 4H), 1.01-0.95 (m, 4H),0.80 (s, 3H). MS: (ES, m/z): 490 [M+H]⁺.

Examples 52 and 53:trans-6-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)spiro[3.3]heptane-2-carboxylicacid andcis-6-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)spiro[3.3]heptane-2-carboxylicacid

Step 1. methyl(2S)-5-amino-6-[[6-(methoxycarbonyl)spiro[3.3]heptan-2-yl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 10-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl 6-aminospiro[3.3]heptane-2-carboxylatehydrochloride (138 mg, 0.67 mmol) was dissolved in dioxane (4 mL). Thenmethyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(100 mg, 0.33 mmol, Intermediate 1), Brettphos (72 mg, 0.13 mmol),3^(rd) Generation BrettPhos precatalyst (61 mg, 0.07 mmol) and sodiumtert-butoxide (97 mg, 1.01 mmol) were added. The resulting solution wasstirred for 1 h at 100° C. under nitrogen atmosphere. The reactionmixture was cooled and the solids were filtered out. The resultingmixture was concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (3:1).This afforded the title compound (76.2 mg, 59%) as an orange oil. MS:(ES, m/z): 388 [M+H]⁺.

Step 2. Synthesis of(7S)-2-benzyl-3-[6-(methoxycarbonyl)spiro[3.3]heptan-2-yl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(2S)-5-amino-6-[[6-(methoxycarbonyl)spiro[3.3]heptan-2-yl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(76.2 mg, 0.20 mmol) was dissolved in dichloromethane (5 mL). Then2-phenylacetaldehyde (70.9 mg, 0.59 mmol) was added. The resultingsolution was stirred for 2 h at room temperature. The resulting mixturewas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (2:1). This affordedthe title compound (43.6 mg, 45%) as an orange solid. MS: (ES, m/z): 488[M+H]⁺.

Step 3. Synthesis oftrans-6-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)spiro[3.3]heptane-2-carboxylicacid andcis-6-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)spiro[3.3]heptane-2-carboxylicacid

Into a 10-mL round-bottom flask, methyl(7S)-2-benzyl-3-[6-(methoxycarbonyl)spiro[3.3]heptan-2-yl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(43.6 mg, 0.09 mmol) was dissolved in tetrahydrofuran (1 mL). Then water(1 mL) was added, followed by lithium hydroxide (10.7 mg, 0.45 mmol).The resulting solution was stirred for 1 h at 85° C. The crude productwas purified by Prep-HPLC with the following conditions: Column, XBridgeC18 OBD Prep Column, 100 Å, 5 μm, 19 mm×250 mm; mobile phase, A: Water(0.1% FA) and B: ACN (10.0% to 25.0% ACN over 24 min); UV Detector: 254nm. This offered the title compounds as follows: 5.4 mg (13%) ofcis-6-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)spiro[3.3]heptane-2-carboxylicacid (assumed stereochemistry, first eluting isomer, RT=21.5 min) as awhite solid and 4.5 mg (11%) oftrans-6-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)spiro[3.3]heptane-2-carboxylicacid (assumed stereochemistry, second eluting isomer, RT=23.0 min) as awhite solid.

First eluting isomer: ¹H-NMR (300 MHz, CD₃OD, ppm): δ 7.42-7.37 (m, 2H),7.38-7.22 (m, 3H), 7.19-7.12 (m, 2H), 4.86-4.72 (m, 2H), 4.39 (s, 2H),3.80 (s, 3H), 3.21-3.10 (m, 1H), 3.10-2.75 (m, 4H), 2.45-2.20 (m, 7H),1.83-1.70 (m, 1H), 1.16 (d, J=6.6 Hz, 3H). MS: (ES, m/z): 474 [M+H]⁺.

Second eluting isomer: ¹H-NMR (300 MHz, CD₃OD, ppm): δ 7.44-7.39 (m,2H), 7.38-7.22 (m, 3H), 7.19-7.12 (m, 2H), 4.78-4.72 (m, 2H), 4.39 (s,2H), 3.80 (s, 3H), 3.21-3.12 (m, 1H), 3.09-2.88 (m, 2H), 2.83-2.76 (m,2H), 2.44-2.20 (m, 7H), 1.77-1.70 (m, 1H), 1.17 (d, J=6.7 Hz, 3H). MS:(ES, m/z): 474 [M+H]⁺.

Examples 54 and 55:cis-3-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclopentane-1-carboxylicacid andtrans-3-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclopentane-1-carboxylicacid

Step 1. Synthesis of methyl(2S)-5-amino-6-[[3-(methoxycarbonyl)cyclopentyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 8-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(300 mg, 1.00 mmol, Intermediate 1) was dissolved in dioxane (5 mL).Then methyl 3-aminocyclopentane-1-carboxylate hydrochloride (540 mg,3.01 mmol), 3^(rd) Generation Brettphos precatalyst (273 mg, 0.30 mmol),BrettPhos (323 mg, 0.60 mmol) and sodium tert-butoxide (385 mg, 4.01mmol) were added. The resulting solution was stirred for 3 h at 100° C.under nitrogen atmosphere. The reaction mixture was cooled to roomtemperature and concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (3:1).This afforded the title compound (130 mg, 36%) as a yellow oil. MS: (ES,m/z): 362 [M+H]⁺.

Step 2. Synthesis of methyl(7S)-2-benzyl-3-[3-(methoxycarbonyl)cyclopentyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(2S)-5-amino-6-[[3-(methoxycarbonyl)cyclopentyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(130 mg, 0.36 mmol) was dissolved in dichloromethane (5 mL). Then2-phenylacetaldehyde (65 mg, 0.54 mmol) was added. The resultingsolution was stirred overnight at room temperature. The resultingmixture was concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (2:1).This afforded the title compound (120 mg, 72%) as a yellow oil. MS: (ES,m/z): 462 [M+H]⁺.

Step 3. Synthesis ofcis-3-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclopentane-1-carboxylicacid andtrans-3-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclopentane-1-carboxylicacid

Into a 25-mL round-bottom flask, was placed methyl(7S)-2-benzyl-3-[3-(methoxycarbonyl)cyclopentyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(142 mg, 0.31 mmol) dissolved in tetrahydrofuran (2 mL). Then water (2mL) was added, followed by lithium hydroxide (37 mg, 1.55 mmol). Theresulting solution was stirred for 2 h at 85° C. The reaction mixturewas cooled and the resulting mixture was concentrated under vacuum. Thecrude product was purified by Prep-HPLC with the following conditions:Column, XBridge C18 OBD Prep Column, 100 mm, 5 μm, 19 mm×250 mm; mobilephase, A: Water (10 mmol/L NH₄HCO₃) and B: ACN (15.0% to 35.0% ACN over7 min); UV Detector: 254 nm. This offered the title compounds asfollows: 23.6 mg (17%) ofcis-3-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclopentane-1-carboxylicacid (assumed stereochemistry, first eluting isomer, RT=5.8 min) as awhite solid and 29.2 mg (21%) oftrans-3-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclopentane-1-carboxylicacid (assumed stereochemistry, second eluting isomer, RT=6.7 min) as awhite solid.

First eluting isomer: ¹H-NMR (300 MHz, CD₃OD, ppm): δ 7.56-7.17 (m, 7H),4.89-4.73 (m, 2H), 4.44 (s, 2H), 3.79 (s, 3H), 3.30-3.18 (m, 1H),3.01-2.90 (m, 1H), 2.89-2.78 (m, 1H), 2.52-2.07 (m, 4H), 2.02-1.70 (m,4H), 1.17 (d, J=6.7 Hz, 3H). MS: (ES, m/z): 448 [M+H]⁺.

Second eluting isomer: ¹H-NMR (300 MHz, CD₃OD, ppm): δ 7.56-7.17 (m,7H), 4.92-4.72 (m, 2H), 4.43 (s, 2H), 3.79 (s, 3H), 3.27-3.19 (m, 1H),3.03-2.93 (m, 1H), 2.87-2.78 (m, 1H), 2.59-2.41 (m, 1H), 2.37-2.12 (m,3H), 2.02-1.90 (m, 2H), 1.82-1.68 (m, 2H), 1.17 (d, J=6.7 Hz, 3H). MS:(ES, m/z): 448 [M+H]⁺.

Examples 56 and 57:trans-4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1R)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid andtrans-4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1S)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid

Step 1. Synthesis of methyl(2S)-5-amino-2-methyl-6-[[trans-4-(methoxycarbonyl)cyclohexyl]amino]-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 25-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, trans-methyl-4-aminocyclohexane-1-carboxylatehydrochloride (259 mg, 1.34 mmol) were dissolved in dioxane (4 mL).Thenmethyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(200 mg, 0.67 mmol, Intermediate 1), Brettphos (144.2 mg, 0.27 mmol),3^(rd) Generation BrettPhos precatalyst (121.6 mg, 0.13 mmol) and sodiumtert-butoxide (193.4 mg, 2.01 mmol) was added successively. Theresulting solution was stirred for 1 h at 100° C. under nitrogenatmosphere. The reaction mixture was cooled and the resulting solidswere filtered out. The filtrate was concentrated under vacuum. Theresidue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (2:1). This afforded the title compound (58.8mg, 23%) as a green oil. MS: (ES, m/z): 376 [M+H]⁺.

Step 2. Synthesis of methyl(7S)-7-methyl-2-(1-phenylethyl)-3-[trans-4-(methoxycarbonyl)cyclohexyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(2S)-5-amino-2-methyl-6-[[trans-4-(methoxycarbonyl)cyclohexyl]amino]-1,2,3,4-tetrahydroquinoline-1-carboxylate(58.8 mg, 0.16 mmol) was dissolved in dichloromethane (5 mL). Then2-phenylpropanal (126 mg, 0.94 mmol) was added. The resulting solutionwas stirred for 3 h at room temperature. The resulting mixture wasconcentrated under vacuum. The residue was subjected to purification byFCC eluting with ethyl acetate/petroleum ether (2:1). This afforded thetitle compound (28.1 mg, 37%) as a yellow solid. MS: (ES, m/z): 490[M+H]⁺.

Step 3. Synthesis oftrans-4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1R)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid and trans-4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1S)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylic acid

Into a 25-mL round-bottom flask, methyl(7S)-7-methyl-2-(1-phenylethyl)-3-[trans-4-(methoxycarbonyl)cyclohexyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(25 mg, 0.05 mmol) was dissolved in tetrahydrofuran (3 mL). Then water(3 mL) was added, followed by lithium hydroxide (6.1 mg, 0.25 mmol). Theresulting solution was stirred for 2 h at 85° C. The resulting mixturewas cooled to room temperature and concentrated under vacuum. The crudeproduct was purified by Prep-HPLC with the following conditions: Column,XBridge Prep C18 OBD Column, 19×150 mm, 5 μm; mobile phase, A: Water(containing 10 mmol/LNH₄HCO₃) and B: ACN (18.0% to 38.0% ACN over 8min); UV Detector: 254 nm. Then the product was purified byChiral-Prep-HPLC with the following conditions: Column, CHIRAL ARTCellulose-SB, 2×25 cm, 5 μm; mobile phase, hexanes (1% TFA) and ethanol(hold 10.0% ethanol in 38 min); Detector, UV 254 nm. This afforded thetitle compounds as follows: 1.4 mg (6%) oftrans-4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1S)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid (assumed stereochemistry, first eluting isomer, RT=25.83 min) as awhite solid and 2.9 mg (12%) oftrans-4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1R)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid (assumed stereochemistry, second eluting isomer, RT=32.76 min) as awhite solid

First eluting isomer: ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.36-7.26 (m,3H), 7.26-7.14 (m, 4H), 4.82-4.75 (m, 1H), 4.39-4.37 (m, 1H), 4.07-4.03(m, 1H), 3.78 (s, 3H), 3.34-3.26 (m, 1H), 3.07-2.02 (m, 1H), 2.40-2.15(m, 5H), 1.98-1.95 (m, 3H), 1.85 (d, J=6.9 Hz, 3H), 1.77-1.69 (m, 2H),1.55-1.42 (m, 1H), 1.17 (d, J=6.6 Hz, 3H). MS: (ES, m/z): 476 [M+H]⁺.

Second eluting isomer: ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.37-7.29 (m,1H), 7.28-7.26 (m, 2H), 7.24-7.17 (m, 4H), 4.81-4.75 (m, 1H), 4.44-4.41(m, 1H), 4.06-4.02 (m, 1H), 3.78 (s, 3H), 3.56-3.27 (m, 1H), 3.06-2.99(m, 1H), 2.40-2.06 (m, 5H), 1.99-1.96 (m, 2H), 1.84 (d, J=6.9 Hz, 3H),1.79-1.70 (m, 3H), 1.49-1.42 (m, 1H), 1.20 (d, J=6.6 Hz, 3H). MS: (ES,m/z): 476 [M+H]⁺.

Examples 58 and 59: methyl(S)-7-methyl-2-((R)-1-phenylethyl)-3-(piperidin-4-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-7-methyl-2-((S)-1-phenylethyl)-3-(piperidin-4-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(2S)-5-amino-6-([1-[(tert-butoxy)carbonyl]piperidin-4-yl]amino)-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 10-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, tert-butyl 4-aminopiperidine-1-carboxylate(402.7 mg, 2.01 mmol) was dissolved in toluene (4 mL). Methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(300 mg, 1.00 mmol, Intermediate 1), BrettPhos (216.2 mg, 0.40 mmol),3^(rd) Generation BrettPhos precatalyst (182.4 mg, 0.20 mmol) and sodiumtert-butoxide (290 mg, 3.02 mmol) were added. The resulting solution wasstirred for 1 h at 100° C. under nitrogen atmosphere. The reactionmixture was cooled and the solids were filtered out. The resultingmixture was concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (2:1).This afforded the title compound (197.1 mg, 47%) as a dark green solid.MS: (ES, m/z): 419 [M+H]⁺.

Step 2. Synthesis of tert-butyl4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1R)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]piperidine-1-carboxylateand tert-butyl4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1S)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]piperidine-1-carboxylate

Into a 25-mL round-bottom flask, methyl(2S)-5-amino-6-([1-[(tert-butoxy)carbonyl]piperidin-4-yl]amino)-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(197.1 mg, 0.47 mmol) was dissolved in dichloromethane (5 mL). Then2-phenylpropanal (379.2 mg, 2.83 mmol) was added. The resulting solutionwas stirred for 3 h at room temperature. The resulting mixture wasconcentrated under vacuum. The residue was subjected to purification byFCC eluting with ethyl acetate/petroleum ether (1:1). This afforded thetitle compounds as follows: 18.1 mg (7%) of tert-butyl4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1R)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]piperidine-1-carboxylateas a yellow solid and 15.6 mg (6%) of tert-butyl4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1S)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]piperidine-1-carboxylateas a yellow solid. MS: (ES, m/z): 533 [M+H]⁺.

Step 3. Synthesis of methyl(S)-7-methyl-2-((R)-1-phenylethyl)-3-(piperidin-4-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-7-methyl-2-((S)-1-phenylethyl)-3-(piperidin-4-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, tert-butyl4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1R)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]piperidine-1-carboxylate(18.1 mg, 0.03 mmol) was dissolved dichloromethane (5 mL). Thentrifluoroacetic acid (1 mL) was added dropwise with stirring. Theresulting solution was stirred for 1.5 h at room temperature.

The resulting mixture was concentrated under vacuum. The crude productwas purified by Prep-HPLC with the following conditions: Column, XBridgeC18 OBD Prep Column, 100 Å, 19 mm×250 mm; mobile phase, A: Water (10mmol/L NH₄HCO₃) and B: ACN (25.0% to 50.0% ACN over 7 min); UV Detector:254 nm. This afforded the title compound (7.7 mg, 52%) as a white solid.¹HNMR: (300 MHz, CD₃OD, ppm): δ 7.51 (d, J=9.0 Hz, 1H), 7.41-7.19 (m,6H), 4.78-4.69 (m, 1H), 4.64-4.58 (m, 1H), 4.38-4.26 (m, 1H), 3.79 (s,3H), 3.40-3.35 (m, 1H), 3.17-3.12 (m, 1H), 2.98-2.88 (m, 2H), 2.68-2.58(m, 1H), 2.48-2.20 (m, 3H), 2.19-2.04 (m, 1H), 1.80 (d, J=7.3 Hz, 3H),1.78-1.68 (m, 2H), 1.19 (d, J=6.6 Hz, 3H), 0.82-0.74 (m, 1H). MS: (ES,m/z): 433 [M+H]⁺.

Into a 25-mL round-bottom flask, tert-butyl4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(1S)-1-phenylethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]piperidine-1-carboxylate(15.6 mg, 0.03 mmol) was dissolved dichloromethane (5 mL). Thentrifluoroacetic acid (1 mL) was added dropwise with stirring. Theresulting solution was stirred for 2 h at room temperature.

The resulting mixture was concentrated under vacuum. The crude productwas purified by Prep-HPLC with the following conditions: Column, XBridgeC18 OBD Prep Column, 100 Å, 19 mm×250 mm; mobile phase, A: Water (10mmol/L NH₄HCO₃) and B: ACN (25.0% to 50.0% ACN over 7 min); UV Detector:254 nm. This afforded the title compounds (7.8 mg, 62%) as a whitesolid. ¹HNMR: (300 MHz, CD₃OD, ppm): δ 7.51 (d, J=9.0 Hz, 1H), 7.41-7.19(m, 6H), 4.78-4.72 (m, 1H), 4.64-4.58 (m, 1H), 4.38-4.26 (m, 1H), 3.79(s, 3H), 3.40-3.35 (m, 1H), 3.17-3.12 (m, 1H), 2.98-2.88 (m, 2H),2.68-2.58 (m, 1H), 2.48-2.20 (m, 3H), 2.19-2.04 (m, 1H), 1.80 (d, J=7.3Hz, 3H), 1.78-1.68 (m, 2H), 1.19 (d, J=6.6 Hz, 3H), 0.82-0.74 (m, 1H).MS: (ES, m/z): 433 [M+H]⁺.

Examples 60 and 61:cis-4-((S)-6-(methoxycarbonyl)-7-methyl-2-((R)-1-phenylpropan-2-yl)-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid andtrans-4-((S)-6-(methoxycarbonyl)-7-methyl-2-((S)-1-phenylpropan-2-yl)-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid

Step 1. Synthesis of methyl(7S)-7-methyl-2-(1-phenylpropan-2-yl)-3-[trans-4-(methoxycarbonyl)cyclohexyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(2S)-5-amino-2-methyl-6-[[trans-4-(methoxycarbonyl)cyclohexyl]amino]-1,2,3,4-tetrahydroquinoline-1-carboxylate(150 mg, 0.40 mmol) was dissolved in dichloromethane (5 mL). Then2-methyl-3-phenylpropanal (178 mg, 1.20 mmol, Intermediate 27) wasadded. The resulting solution was stirred for 3 h at room temperature.The resulting mixture was concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:2). This afforded the title compound (150 mg, 72%) as a yellowoil. MS: (ES, m/z): 504 [M+H]⁺.

Step 2. Synthesis ofcis-4-((S)-6-(methoxycarbonyl)-7-methyl-2-((R)-1-phenylpropan-2-yl)-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid andtrans-4-((S)-6-(methoxycarbonyl)-7-methyl-2-((S)-1-phenylpropan-2-yl)-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid

Into a 50-mL round-bottom flask, methyl(7S)-7-methyl-2-(1-phenylpropan-2-yl)-3-[trans-4-(methoxycarbonyl)cyclohexyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(150 mg, 0.30 mmol) was dissolved in tetrahydrofuran (5 mL). Water (5mL) was added, followed by lithium hydroxide (36 mg, 1.50 mmol). Theresulting solution was stirred for 1 h at 85° C. The resulting mixturewas cooled and concentrated under vacuum. The crude product was purifiedby Prep-HPLC with the following conditions: Column, XBridge Shield RP18OBD Column, 5 μm, 19×150 mm; mobile phase, A: Water (containing 10mmol/L NH₄HCO₃) and B: ACN (10.0% to 67.0% ACN over 5 min); UV Detector:254 nm. The crude product was purified by Chiral-Prep-HPLC with thefollowing conditions: Column, CHIRALPAK IE, 2×25 cm,5 μm; mobile phase,A: hexanes (0.1% FA) and B: ethanol (hold 35.0% ethanol in 10 min); UVDetector: 254 nm. This afforded the title compounds as follows: 42.1 mg(28%) oftrans-4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(2R)-1-phenylpropan-2-yl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid (assumed stereochemistry, first eluting isomer) as a white solidand 23.1 mg (15%) oftrans-4-[(7S)-6-(methoxycarbonyl)-7-methyl-2-[(2S)-1-phenylpropan-2-yl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid (assumed stereochemistry, second eluting isomer) as a white solid.

First eluting isomer: ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.37 (d, J=9.0Hz, 1H), 7.29 (d, J=8.9 Hz, 1H), 7.22-6.98 (m, 5H), 4.80-4.67 (m, 1H),4.08-3.97 (m, 1H), 3.77 (s, 3H), 3.68-3.54 (m, 1H), 3.24-2.87 (m, 4H),2.43-1.88 (m, 6H), 1.79-1.50 (m, 6H), 1.39-1.07 (m, 4H), 0.59-0.56 (m,1H). MS: (ES, m/z): 490 [M+H]⁺.

Second eluting isomer: ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.42-7.27 (m,2H), 7.19-7.01 (m, 5H), 4.80-4.65 (m, 1H), 4.18-4.03 (m, 1H), 3.75 (s,3H), 3.68-3.53 (m, 1H), 3.28-3.04 (m, 3H), 3.00-2.84 (m, 1H), 2.46-1.90(m, 6H), 1.83-1.57 (m, 3H), 1.51 (d, J=6.8 Hz, 3H), 1.41-1.24 (m, 1H),1.16 (d, J=6.6 Hz, 3H), 0.75-0.72 (m, 1H). MS: (ES, m/z): 490 [M+H]⁺.

Examples 62 and 63:(1S,3R)-3-((S)-6-(methoxycarbonyl)-7-methyl-2-phenethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid and(1R,3S)-3-((S)-6-(methoxycarbonyl)-7-methyl-2-phenethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid

Step 1. Synthesis of methyl(2S)-5-amino-6-[[cis-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 10-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl cis-3-aminocyclohexane-1-carboxylatehydrochloride (260 mg, 1.34 mmol) was dissolved in dioxane (4 mL). Thenmethyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(200 mg, 0.66 mmol, Intermediate 1), Brettphos (144 mg, 0.26 mmol),Brettphos Pd G3 (122 mg, 0.14 mmol) and sodium tert-butoxide (194 mg,2.02 mmol) were added. The resulting solution was stirred for 1 h at100° C. under nitrogen atmosphere. The reaction mixture was cooled andthe solids were filtered out. The resulting mixture was concentratedunder vacuum. The residue was subjected to purification by FCC elutingwith ethyl acetate/petroleum ether (2:1). This afforded the titlecompound (125.5 mg, 50%) as a green oil. MS: (ES, m/z): 376 [M+H]⁺.

Step 2. Synthesis of methyl(7S)-3-[cis-3-(methoxycarbonyl)cyclohexyl]-7-methyl-2-(2-phenylethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(2S)-5-amino-6-[[cis-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(125.5 mg, 0.33 mmol) was dissolved in dichloromethane (5 mL). Then3-phenylpropanal (134.5 mg, 1.00 mmol) was added. The resulting solutionwas stirred for 2 h at room temperature. The resulting mixture wasconcentrated under vacuum. The residue was subjected to purification byFCC eluting with ethyl acetate/petroleum ether (2:1). This afforded thetitle compound (105.1 mg, 64%) as a green solid. MS: (ES, m/z): 490[M+H]⁺.

Step 3. Synthesis of(1S,3R)-3-((S)-6-(methoxycarbonyl)-7-methyl-2-phenethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid and(1R,3S)-3-((S)-6-(methoxycarbonyl)-7-methyl-2-phenethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid

Into a 25-mL round-bottom flask, methyl(7S)-3-[cis)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-2-(2-phenylethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(105.1 mg, 0.21 mmol) was dissolved in tetrahydrofuran (2 mL). Thenwater (2 mL) was added, followed by lithium hydroxide (25.8 mg, 1.08mmol). The resulting solution was stirred for 2 h at 85° C. Theresulting mixture was concentrated under vacuum. The crude product waspurified by Prep-HPLC with the following conditions: Column, XBridgeShield RP18 OBD Column, 5 μm, 19×150 mm; mobile phase, A: water (10mmol/L NH₄HCO₃) and B: ACN (20.0% to 45.0% ACN over 7 min); UV Detector:254 nm. This afforded the title compounds as follow: 22.7 mg (22%) ofSynthesis of(1S,3R)-3-((S)-6-(methoxycarbonyl)-7-methyl-2-phenethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid (assumed stereochemistry, first eluting isomer, RT=4.8 min) as awhite solid and 22.7 mg (22%) of(1R,3S)-3-((S)-6-(methoxycarbonyl)-7-methyl-2-phenethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid (assumed stereochemistry, second eluting isomer, RT=5.9 min) as awhite solid.

First eluting isomer: ¹H-NMR: (400 MHz, CD₃OD, ppm): δ 7.47-7.34 (m,2H), 7.31-7.14 (m, 5H), 4.78-4.70 (m, 1H), 4.18-4.12 (m, 1H), 3.79 (s,3H), 3.26-3.23 (m, 2H), 3.20-3.09 (m, 3H), 2.94-2.87 (m, 1H), 2.42-2.36(m, 1H), 2.33-2.17 (m, 2H), 2.16-1.96 (m, 2H), 1.92-1.84 (m, 1H),1.82-1.65 (m, 2H), 1.48-1.38 (m, 3H), 1.15 (d, J=6.8 Hz, 3H). MS: (ES,m/z): 476 [M+H]⁺.

Second eluting isomer: ¹H-NMR: (400 MHz, CD₃OD, ppm): δ 7.48-7.33 (m,2H), 7.31-7.13 (m, 5H), 4.78-4.70 (m, 1H), 4.17-4.10 (m, 1H), 3.78 (s,3H), 3.25-3.22 (m, 2H), 3.26-3.07 (m, 3H), 2.95-2.87 (m, 1H), 2.46-2.35(m, 1H), 2.34-2.19 (m, 2H), 2.12-1.96 (m, 2H), 1.94-1.88 (m, 1H),1.76-1.66 (m, 1H), 1.57-1.40 (m, 4H), 1.15 (d, J=6.8, 2.1 Hz, 3H).

Examples 64 and 65:(1R,3R)-3-((S)-6-(methoxycarbonyl)-7-methyl-2-phenethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid and(1S,3S)-3-((S)-6-(methoxycarbonyl)-7-methyl-2-phenethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid

Step 1. Synthesis of methyl(2S)-5-amino-6-[[trans-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 10-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, trans-methyl-3-aminocyclohexane-1-carboxylatehydrochloride (260 mg, 1.34 mmol) was dissolved in dioxane (4 mL). Thenmethyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(200 mg, 0.66 mmol, Intermediate 1), Brettphos (144 mg, 0.26 mmol),3^(rd) Generation BrettPhos precatalyst (122 mg, 0.14 mmol) and sodiumtert-butoxide (194 mg, 2.02 mmol) were added. The resulting solution wasstirred for 1 h at 100° C. under nitrogen atmosphere. The reactionmixture was cooled and the resulting solids were filtered out. Thefiltrate was concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (2:1).This afforded the title compound (80 mg, 45%) as green oil. MS: (ES,m/z): 376 [M+H]⁺.

Step 2. Synthesis of methyl(7S)-3-[trans-3-(methoxycarbonyl)cyclohexyl]-7-methyl-2-(2-phenylethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask, methyl(2S)-5-amino-6-[[trans-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(80 mg, 0.21 mmol) was dissolved in dichloromethane (5 mL). Then3-phenylpropanal (57 mg, 0.42 mmol) was added. The resulting solutionwas stirred for 1 h at room temperature. The resulting mixture wasconcentrated under vacuum. The residue was subjected to purification byFCC eluting with ethyl acetate/petroleum ether (1:1). This afforded thetitle compound 75 mg (72%) as a yellow solid. MS: (ES, m/z): 490 [M+H]⁺.

Step 3. Synthesis of(1R,3R)-3-((S)-6-(methoxycarbonyl)-7-methyl-2-phenethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid and(1S,3S)-3-((S)-6-(methoxycarbonyl)-7-methyl-2-phenethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)cyclohexane-1-carboxylicacid

Into a 50-mL round-bottom flask, methyl(7S)-3-[trans-3-(methoxycarbonyl)cyclohexyl]-7-methyl-2-(2-phenylethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(75 mg, 0.15 mmol) was dissolved in tetrahydrofuran (2 mL). Water (2 mL)was added, followed by lithium hydroxide (18.3 mg, 0.76 mmol). Theresulting solution was stirred for 2 h at 85° C. The resulting mixturewas concentrated under vacuum. The crude product was purified byPrep-HPLC with the following conditions: Column, XBridge C18 OBD PrepColumn, 100 Å, 5 μm, 19 mm×250 mm; mobile phase, A: water (0.05% NH₄OH)and B: ACN (20.0% to 40.0% ACN over 12 min); UV Detector: 254 nm. Thisafforded the title compounds as follows: 2.6 mg (4%) of(1R,3R)-3-[(7S)-6-(methoxycarbonyl)-7-methyl-2-(2-phenylethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid (assumed stereochemistry, first eluting isomer, RT=8.9 min) as awhite solid and 2.4 mg (3%) of(1S,3S)-3-[(7S)-6-(methoxycarbonyl)-7-methyl-2-(2-phenylethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid (assumed stereochemistry, second eluting isomer, RT=11.2 min) as awhite solid.

First eluting isomer: 1H NMR (Methanol-d4, 400 MHz) δ (ppm): 7.47-7.45(m, 1H), 7.36-7.33 (m, 1H), 7.25-7.24 (m, 4H), 7.19-7.16 (m, 1H),4.76-4.72 (m, 1H), 4.64-4.59 (m, 2H), 3.76 (s, 3H), 3.26-3.11 (m, 3H),3.02-2.88 (m, 3H), 2.33-2.20 (m, 5H), 1.76-1.70 (m, 3H), 1.48-1.48 (m,2H), 1.13 (d, J=6.8 Hz, 3H). MS: (ES, m/z): 476 [M+H]⁺.

Second eluting isomer: 1H NMR (Methanol-d4, 400 MHz) δ (ppm): 7.49-7.47(m, 1H), 7.38-7.36 (m, 1H), 7.26-7.25 (m, 4H), 7.20-7.16 (m, 1H),4.77-4.68 (m, 3H), 3.76 (s, 3H), 3.26-3.11 (m, 3H), 3.01-2.88 (m, 3H),2.37-2.20 (m, 5H), 1.78-1.70 (m, 3H), 1.57-1.51 (m, 2H), 1.13 (d, J=6.8Hz, 3H). MS: (ES, m/z): 476 [M+H]⁺.

Example 66: methyl(S)-2-benzyl-3-((3R,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(2S)-5-amino-6-[[(3R,6S)-6-[[(tert-butyldimethylsilyl)oxy]methyl]oxan-3-yl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 50-mL round-bottom flask, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(120 mg, 0.40 mmol, Intermediate 1) was dissolved in toluene (5 mL).Then (3R,6S)-6-[[(tert-butyldimethylsilyl)oxy]methyl]oxan-3-amine (292mg, 1.19 mmol, Intermediate 30), Brettphos (86 mg, 0.16 mmol, 0.40equiv), 3rd Generation Brettphos precatalyst (72 mg, 0.08 mmol) andsodium tert-butoxide (76 mg, 0.79 mmol) were added. The resultingsolution was stirred for 2 h at 110° C. under nitrogen atmosphere. Thereaction mixture was cooled and the resulting solids were filtered out.The filtrate was concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (1:1).This afforded the title compound (90 mg, 48%) as a brown oil. MS: (ES,m/z): 464 [M+H]⁺.

Step 2. Synthesis of methyl(7S)-2-benzyl-3-[(3R,6S)-6-[[(tert-butyldimethylsilyl)oxy]methyl]oxan-3-yl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask, methyl(2S)-5-amino-6-[[(3R,6S)-6-[[(tert-butyldimethylsilyl)oxy]methyl]oxan-3-yl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(90 mg, 0.19 mmol) was dissolved in dichloromethane (5 mL). Then2-phenylacetaldehyde (23 mg, 0.19 mmol) was added. The resultingsolution was stirred for 12 h at room temperature. The reaction mixturewas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (1:2). This affordedthe title compound (70 mg, 64%) as a light yellow solid. MS: (ES, m/z):564 [M+H]⁺.

Step 3. Synthesis of (S)-methyl2-benzyl-3-((3R,6S)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3-yl)-7-methyl-8,9-dihydro-3H-imidazo[4,5-f]quinoline-6(7H)-carboxylate

Into a 50-mL round-bottom flask, methyl(7S)-2-benzyl-3-[(3R,6S)-6-[[(tert-butyldimethylsilyl)oxy]methyl]oxan-3-yl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(30 mg, 0.05 mmol) was dissolved in tetrahydrofuran (3 mL). Thentetrabutylammonium fluoride (1 M in THF, 0.08 mL, 0.08 mmol) was added.The resulting solution was stirred for 1 h at room temperature. Thereaction mixture was concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:1). The crude product was purified by Prep-HPLC with thefollowing conditions:

Column, XBridge C18 OBD Prep Column, 100 Å, 5 μm, 19 mm×250 mm; mobilephase, A: Water (containing 0.05% TFA) and B: ACN (5.0% to 60.0% ACNover 30 min); UV Detector: 254 nm. This afforded the title compound (3.3mg, 14%) as a yellow oil.

¹H-NMR: (CDCl₃, 300 MHz) δ (ppm): 7.85-7.81 (m, 1H), 7.41-7.29 (m, 6H),4.86-4.77 (m, 2H), 4.61-4.51 (m, 3H), 4.10-4.03 (m, 1H), 3.84-3.81 (m,4H), 3.69-3.56 (m, 3H), 3.18-3.15 (m, 2H), 2.38-2.33 (m, 1H), 2.20-2.14(m, 1H), 1.91-1.85 (m, 1H), 1.79-1.75 (m, 1H), 1.63-1.59 (m, 1H),1.46-1.42 (m, 1H), 1.15 (d, J=6.6 Hz, 3H). MS: (ES, m/z): 450 [M+H]⁺.

The following examples in TABLE 4 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Example 66.

TABLE 4 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 67

451 ¹H-NMR (DMSO-d6, 400 MHz) δ (ppm): 7.66-7.64 (m, 1H), 7.55- 7.49 (m,2H), 7.45-7.43 (m, 1H), 6.62-6.60 (m, 1H), 6.42-6.38 (m, 1H), 5.58-5.48(m, 2H), 4.75-4.66 (m, 2H), 3.76 (s, 3H), 3.70-3.66 (m, 1H), 3.17-3.13(m, 1H), 2.94- 2.90 (m, 1H), 2.23-2.10 (m, 3H), 2.0-1.88 (m, 3H),1.75-1.67 (m, 2H), 1.42-1.39 (m, 1H), 1.36-1.28 (m, 1H), 1.13 (d, J =6.8 Hz, 3H) 68

451 ¹H-NMR (DMSO-d6, 400 MHz) δ (ppm): 7.66-7.64 (m, 1H), 7.55- 7.49 (m,2H), 7.45-7.43 (m, 1H), 6.62-6.60 (m, 1H), 6.42-6.38 (m, 1H), 5.58-5.48(m, 2H), 4.75-4.66 (m, 2H), 3.76 (s, 3H), 3.70-3.66 (m, 1H), 3.17-3.13(m, 1H), 2.94- 2.90 (m, 1H), 2.23-2.10 (m, 3H), 2.0-1.88 (m, 3H),1.75-1.67 (m, 2H), 1.42-1.39 (m, 1H), 1.36-1.28 (m, 1H), 1.13 (d, J =6.8 Hz, 3H) 69

451 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.69-7.67 (m, 1H), 7.56- 7.49 (m,2H), 7.42-7.40 (m, 1H), 6.59-6.57 (m, 1H), 6.42-6.39 (m, 1H), 5.68-5.64(m, 1H), 5.35-5.32 (m, 1H), 4.98-4.85 (m, 1H), 4.73- 4.71 (m, 1H),4.28-4.26 (m, 1H), 3.75 (s, 3H), 3.13-3.11 (m, 1H), 2.89-2.85 (m, 1H),2.52-2.50 (m, 1H), 2.25-2.18 (m, 2H), 1.98-1.82 (m, 2H), 1.71-1.69 (m,2H), 1.68- 1.64 (m, 3H), 1.11 (d, J = 6.4 Hz, 3H) 70

451 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.66-7.64 (m, 1H), 7.55- 7.49 (m,2H), 7.45-7.43 (m, 1H), 6.62-6.60 (m, 1H), 6.42-6.38 (m, 1H), 5.58-5.47(m, 2H), 4.75-4.66 (m, 2H), 3.76 (s, 3H), 3.70-3.68 (m, 1H), 3.17-3.13(m, 1H), 2.95- 2.91 (m, 1H), 2.22-2.11 (m, 3H), 2.09-2.00 (m, 2H),1.87-1.75 (m, 1H), 1.73-7.64 (m, 2H), 1.52- 1.37 (m, 2H), 1.12 (d, J =6.8 Hz, 3H) 71

451 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.47-7.44 (m, 2H), 7.34- 7.27 (m,2H), 6.64-6.61 (m, 1H), 6.16-6.11 (m, 1H), 5.67-5.62 (m, 1H), 5.45-5.40(m, 1H), 4.81-4.79 (m, 1H), 4.68-4.65 (m, 1H), 3.77- 3.72 (m, 4H),3.21-3.12 (m, 1H), 3.05-3.01 (m, 1H), 2.25-2.17 (m, 3H), 2.11-2.05 (m,2H), 1.76-1.72 (m, 2H), 1.60-1.49 (m, 3H), 1.17 (d, J = 6.9 Hz, 3H)

Example 72:(2S,5R)-5-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)tetrahydro-2H-pyran-2-carboxylicacid

Step 1. Synthesis of(2S,5R)-5-((S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)tetrahydro-2H-pyran-2-carboxylicacid

Into a 50-mL round-bottom flask, was placed methyl(7S)-2-benzyl-3-[(3R,6S)-6-(hydroxymethyl)oxan-3-yl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(20 mg, 0.04 mmol, 1.00 equiv), water (1.5 mL), CH₃CN (1 mL),dichloromethane (1 mL), NaIO₄ (47 mg, 0.22 mmol, 4.94 equiv), andRuCl₃.H₂O (5 g, 22.18 mmol) was added at 0° C. The resulting solutionwas stirred for 12 h at room temperature. The solids were filtered out.The product was purified with the following conditions: Column: XBridgeShield RP18 OBD Column, 5 um, 19×150 mm; Mobile Phase A: Water (0.1%FA), Mobile Phase B: ACN; Flow rate: 20 mL/min; Gradient: 25% B to 55% Bin 7 min; 254 nm; RT: 6.5 min. This resulted in 1.3 mg (6%) of(2S,5R)-5-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]oxane-2-carboxylicacid as a yellow solid. ¹H-NMR: (300 MHz, CDCl₃, ppm): 7.47-7.45 (m,1H), 7.27-7.18 (m, 6H), 4.84-4.80 (m, 1H), 4.54-4.49 (m, 1H), 4.37-4.27(m, 2H), 4.12-4.05 (m, 2H), 3.94-3.92 (m, 1H), 3.80 (s, 1H), 3.25-3.20(m, 1H), 3.10-3.08 (m, 1H), 2.37-2.32 (m, 2H), 1.78-1.76 (m, 1H),1.61-1.53 (m, 2H), 1.44-1.42 (m, 1H), 1.18-1.16 (m, 3H). MS: (ES, m/z):464 [M+H]⁺.

Example 73: methyl(S)-2-benzyl-3-((3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(S)-2-benzyl-3-((3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask, was placed(2S,5R)-5-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]oxane-2-carboxylicacid (20 mg, 0.04 mmol), N,N-dimethylformamide (2 mL), HATU (32 mg, 0.08mmol), NMM (18 mg, 0.18 mmol), NH₄Cl (4 mg, 0.07 mmol). The resultingsolution was stirred for 1 h at room temperature. The product waspurified with the following conditions: Column: XBridge Shield RP18 OBDColumn, 5 um,19*150 mm; Mobile Phase A: Water (10 mmol/L NH₄HCO₃),Mobile Phase B: ACN; Flow rate: 20 mL/min; Gradient: 25% B to 75% B in 7min; 254 nm; RT: 6.5 min. This resulted in 1.5 mg (8%) of methyl(7S)-2-benzyl-3-[(3R,6S)-6-carbamoyloxan-3-yl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateas a white solid. ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.55-7.53 (m, 1H),7.46-7.45 (m, 1H), 7.35-7.30 (m, 2H), 7.24-7.22 (m, 3H), 4.79-4.74 (m,1H), 4.47-4.43 (m, 3H), 4.17-4.11 (m, 1H), 4.06-4.02 (m, 1H), 3.76-3.70(m, 4H), 3.23-3.15 (m, 1H), 2.98-2.95 (m, 1H), 2.54-2.46 (m, 1H),2.28-2.15 (m, 2H), 1.78-1.61 (m, 2H), 1.48-1.42 (m, 1H), 1.13 (d, J=6.6Hz, 3H). MS: (ES, m/z): 463 [M+H]⁺.

Example 74: methyl(7S)-2-benzyl-7-methyl-3-[trans-4-carbamoylcyclohexyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(7S)-2-benzyl-7-methyl-3-[trans-4-carbamoylcyclohexyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask,trans-4-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid (30 mg, 0.07 mmol) was dissolved in methanol (3 mL). Then ammoniumchloride (15.8 mg, 0.30 mmol),4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methyl morpholinium chloride(61.6 mg, 0.22 mmol) and triethylamine (15 mg, 0.15 mmol) were added.The resulting solution was stirred for overnight at room temperature.The crude product was purified by Prep-HPLC with the followingconditions: Column, XBridge C18 OBD Prep Column, 100 Å, 5 μm, 19 mm×250mm; mobile phase, A: water (10 mmol/L NH₄HCO₃) and B: ACN (22.0% to38.0% ACN over 10 min); UV Detector: 254 nm. This offered the titlecompound (10.9 mg, 32%) as a white solid.

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.50-7.21 (m, 7H), 4.79-4.72 (m, 1H),4.43 (s, 2H), 4.37-4.21 (m, 1H), 3.79 (s, 3H), 3.33-3.15 (m, 1H),2.99-2.90 (m, 1H), 2.39-2.14 (m, 4H), 1.92-1.82 (m, 2H), 1.80-1.70 (m,1H), 1.59-1.40 (m, 4H), 1.17 (d, J=6.7 Hz, 3H). MS: (ES, m/z): 461[M+H]⁺.

The following examples in TABLE 5 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Example 74.

TABLE 5 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 75

461 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.52 (d, J = 9.0 Hz, 1H), 7.41-7.22(m, 6H), 4.81- 4.73 (m, 1H), 4.41 (s, 2H), 4.36-4.25 (m, 1H), 3.79 (s,3H), 3.32-3.15 (m, 1H), 3.00- 2.92 (m, 1H), 2.70-2.50 (m, 3H), 2.37-2.19(m, 1H), 2.12- 2.02 (m, 2H), 1.86-1.71 (m, 1H), 1.60-1.47 (m, 2H), 1.36-1.22 (m, 2H), 1.17 (d, J = 6.7 Hz, 3H) 76

475 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.43-7.30 (m, 2H), 7.27-7.25 (m,2H), 7.21-7.17 (m, 3H), 4.78-4.75 (m, 1H), 4.15-4.11 (m, 1H), 3.79 (s,3H), 3.16-3.10 (m, 5H), 2.97- 2.89 (m, 1H), 2.39-2.20 (m, 4H), 1.99-1.95(m, 2H), 1.62- 1.58 (m, 5H), 1.16 (d, J = 6.9 Hz, 3H) 77

475 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.52-7.49 (m, 1H), 7.33-7.25 (m,3H), 7.20-7.17 (m, 3H), 4.79-4.73 (m, 1H), 4.22-4.15 (m, 1H), 3.78 (s,3H), 3.34-3.09 (m, 5H), 2.92- 2.88 (m, 1H), 2.64-2.60 (m, 3H), 2.26-2.11(m, 3H), 1.77- 1.70 (m, 3H), 1.41-1.29 (m, 2H), 1.16 (d, J = 6.9 Hz, 3H)

Example 78: methyl(S)-3-(azetidin-3-yl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(2S)-5-amino-6-([1-[(tert-butoxy)carbonyl]azetidin-3-yl]amino)-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 10-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(100 mg, 0.33 mmol, Intermediate 1) was dissolved in toluene (3 mL).Then tert-butyl 3-aminoazetidine-1-carboxylate (173.2 mg, 1.01 mmol),Brettphos (36 mg, 0.07 mmol), 3^(rd) Generation BrettPhos precatalyst(60.8 mg, 0.07 mmol) and sodium tert-butoxide (96.6 mg, 1.01 mmol) wereadded. The resulting solution was stirred for 1 h at 100° C. undernitrogen atmosphere. The reaction mixture was cooled to room temperatureand the solids were filtered out. The filtrate was concentrated undervacuum. The residue was subjected to purification by FCC eluting withethyl acetate/petroleum ether (2:1). This afforded the title compound(58 mg, 44%) as a brown solid. MS: (ES, m/z): 391 [M+H]⁺.

Step 2. Synthesis of tert-butyl3-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]azetidine-1-carboxylate

Into a 25-mL round-bottom flask, methyl(2S)-5-amino-6-([1-[(tert-butoxy)carbonyl]azetidin-3-yl]amino)-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(58 mg, 0.15 mmol) was dissolved in dichloromethane (5 mL). Then2-phenylacetaldehyde (107 mg, 0.89 mmol) was added. The resultingsolution was stirred for 4 h at room temperature. The resulting mixturewas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (2:1). This affordedthe title compound (43.3 mg, 59%) as a yellow oil. MS: (ES, m/z): 491[M+H]⁺.

Step 3. Synthesis of methyl(S)-3-(azetidin-3-yl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, tert-butyl3-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]azetidine-1-carboxylate(43.3 mg, 0.09 mmol) was dissolved in dichloromethane (5 mL). Thentrifluoroacetic acid (1.5 mL) was added. The resulting solution wasstirred for 3 h at room temperature. The resulting mixture wasconcentrated under vacuum. The crude product was purified by Prep-HPLCwith the following conditions: Column, XBridge C18 OBD Prep Column, 100Å, 5 um, 19 mm×250 mm; mobile phase, A: Waters (containing 10 mmol/LNH₄HCO₃) and B: ACN (25.0% to 45.0% ACN over 7 min); UV Detector: 254nm. This afforded the title compounds (6 mg, 17%) of as a white solid.¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.84 (d, J=9.0 Hz, 1H), 7.52 (d, J=8.9Hz, 1H), 7.37-7.21 (m, 3H), 7.19-7.12 (m, 2H), 5.45-5.35 (m, 1H),4.82-4.76 (m, 1H), 4.45-4.22 (m, 4H), 3.81 (s, 3H), 3.72-3.64 (m, 2H),3.28-3.49 (m, 1H), 3.02-2.94 (m, 1H), 2.32-2.24 (m, 1H), 1.85-1.75 (m,1H), 1.18 (d, J=6.7 Hz, 3H). MS: (ES, m/z): 391 [M+H]⁺.

The following examples in TABLE 6 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Example 78.

TABLE 6 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 79

405 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49-7.18 (m, 7H), 5.04-4.99 (m,1H), 4.79-4.74 (m, 1H), 4.46 (s, 2H), 3.79 (s, 3H), 3.32-3.12 (m, 3H),3.07-2.91 (m, 3H), 2.35-2.12 (m, 2H), 1.92-1.86 (m, 1H), 1.78-1.71 (m,1H), 1.17 (d, J = 6.7 Hz, 3H) 80

405 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.49-7.17 (m, 7H), 5.05-4.95 (m,1H), 4.80-4.74 (m, 1H), 4.46 (s, 2H), 3.80 (s, 3H), 3.33-3.16 (m, 2H),3.14-2.83 (m, 4H), 2.38-2.13 (m, 2H), 2.04-1.86 (m, 1H), 1.86-1.69 (m,1H), 1.17 (d, J = 6.7 Hz, 3H) 81

445 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.44-7.11 (m, 7H), 4.78-4.62 (m,2H), 3.82-3.74 (m, 6H), 3.29-2.88 (m, 9H), 2.62-2.50 (m, 2H), 2.28-2.20(m, 1H), 1.74-1.70 (m, 1H), 1.15 (d, J = 6.7 Hz, 3H) 82

445 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.39-7.36 (m, 1H), 7.35-7.30 (m,1H), 7.30-7.18 (m, 5H), 4.81-4.77 (m, 1H), 4.41-4.27 (m, 2H), 4.03-3.99(m, 1H), 3.78 (s, 3H), 3.27-3.21 (m, 1H), 3.09- 3.02 (m, 1H), 2.89-2.83(m, 4H), 2.28-2.19 (m, 3H), 1.82-1.68 (m, 5H), 1.37-1.35 (m, 3H),1.18-1.16 (m, 4H), 1.04-0.96 (m, 2H) 83

445 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.38 (d, J = 8.8 Hz, 1H), 7.35-7.13(m, 6H), 4.82-4.77 (m, 1H), 4.70-4.60 (m, 1H), 4.44-4.28 (m, 2H), 3.79(s, 3H), 3.70-3.61 (m, 2H), 3.29-3.22 (m, 1H), 3.07-3.02 (m, 1H),2.28-2.20 (m, 1H), 2.11-2.04 (m, 1H), 2.00-1.72 (m, 9H), 1.17 (d, J =6.8 Hz, 3H) 84

431 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.56-7.42 (m, 2H), 7.41-7.18 (m,5H), 4.84-4.72 (m, 2H), 4.52-4.36 (m, 2H), 3.84-3.78 (m, 4H), 3.30-3.18(m, 1H), 3.10-2.93 (m, 2H), 2.50-2.40 (m, 1H), 2.32-2.20 (m, 1H),2.14-1.94 (m, 2H), 1.85-1.65 (m, 3H), 1.50-1.40 (m, 1H), 1.18-1.12 (m,3H). 85

431 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.47 (d, J = 1.4 Hz, 2H), 7.40-7.20(m, 3H), 7.20-7.10 (m, 2H), 4.82-4.76 (m, 1H), 4.52 (d, J = 2.3 Hz, 2H),4.19- 4.08 (m, 2H), 3.80 (s, 3H), 3.31-3.13 (m, 2H), 3.07-2.94 (m, 2H),2.72-2.68 (m, 1H), 2.35-2.17 (m, 1H), 1.82-1.50 (m, 5H), 1.18-1.14 (m,3H) 86

433 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.35 (d, J = 8.7 Hz, 1H), 7.31-7.19(m, 5H), 7.11 (d, J = 8.7 Hz, 1H), 4.89-3.71 (m, 1H), 4.43-4.28 (m, 2H),3.89-3.67 (m, 5H), 3.27-3.22 (m, 1H), 3.08-2.81 (m, 3H), 2.60-2.57 (m,1H), 2.33-2.23 (m, 2H), 1.94-1.61 (m, 5H), 1.42-1.28 (m, 1H), 1.19-1.11(m, 4H) 87

433 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.84 (d, J = 9.2 Hz, 1H), 7.62 (d,J = 9.2 Hz, 1H), 7.45-7.42 (m, 2H), 7.39- 7.34 (m, 3H), 4.87-4.83 (m,1H), 4.63- 4.61 (m, 2H), 4.36 (d, J = 7.6 Hz, 2H), 3.82 (s, 3H),3.33-3.32 (m, 1H), 3.25- 3.22 (m, 2H), 3.14-2.98 (m, 1H), 2.89- 2.77 (m,2H), 2.32-2.25 (m, 2H), 1.94- 1.85 (m, 2H), 1.74-1.71 (m, 1H), 1.61-1.57 (m, 1H), 1.37-1.33 (m, 1H), 1.18 (d, J = 6.8 Hz, 3H) 88

433 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.46 (d, J = 8.8 Hz, 1H), 7.34-7.18(m, 6H), 4.86-4.79 (m, 1H), 4.43 (q, J = 15.9 Hz, 2H), 3.91-3.88 (m,2H), 3.81 (s, 3H), 3.33-3.30 (m, 1H), 3.11-2.93 (m, 2H), 2.76-2.73 (m,1H), 2.46-2.21 (m, 2H), 1.82-1.73 (m, 2H), 1.59-1.41 (m, 3H), 1.21 (d, J= 6.6 Hz, 5H) 89

433 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.32 (d, J = 9.0 Hz, 1H), 7.30-7.16(m, 6H), 4.83-4.77 (m, 1H), 4.39 (s, 2H), 3.81 (d, J = 6.6 Hz, 2H), 3.78(s, 3H), 3.31-3.22 (m, 1H), 3.08-2.92 (m, 2H), 2.66-2.64 (m, 1H),2.38-2.23 (m, 2H), 1.79-1.70 (m, 2H), 1.56-1.52 (m, 2H), 1.46-1.38 (m,1H), 1.24-1.16 (m, 5H) 90

419 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.54 (d, J = 9.0 Hz, 1H), 7.46-7.20(m, 6H), 4.84-4.78 (m, 1H), 4.42-4.30 (m, 3H), 3.79 (s, 3H), 3.29-3.19(m, 1H), 3.14-2.91 (m, 3H), 2.59-2.48 (m, 2H), 2.38-2.20 (m, 3H),1.80-1.72 (m, 1H), 1.45-1.35 (m, 2H), 1.17 (d, J = 6.7 Hz, 3H) 91

419 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.39 (d, J = 8.8 Hz, 1H), 7.30-7.17(m, 6H), 4.82-4.78 (m, 1H), 4.46-4.24 (m, 3H), 378 (s, 3H), 3.32-3.02(m, 4H), 2.92-2.85 (m, 1H), 2.63-2.58 (m, 1H), 2.30-2.11 (m, 2H).1.75-1.73 (m, 2H), 1.43-1.38 (m, 2H), 1.17 (d, J = 6.8 Hz, 3H) 92

419 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.55-7.20 (m, 7H), 4.82-4.78 (m,1H), 4.52-4.31 (m, 3H), 3.79 (s, 3H), 3.36- 3.34 (m, 1H), 3.28-3.15 (m,1H), 3.01-2.92 (m, 2H), 2.87-2.80 (m, 1H), 2.68-2.58 (m, 1H), 2.30-2.12(m, 2H), 1.81-1.71 (m, 2H), 1.48-1.40 (m, 2H), 1.17 (d, J = 6.6 Hz, 3H)93

433 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.43 (d, J = 8.4 Hz, 1H), 7.31-7.19(m, 5H), 7.06 (d, J = 8.8 Hz, 1H), 4.83-4.78 (m, 1H), 4.41-4.29 (m, 2H),3.80 (d, J = 8 Hz, 5H), 3.31-3.01 (m, 4H), 2.47-2.23 (m, 3H), 1.77-1.72(m, 6H), 1.60 (s, 3H) 94

431 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.43 (d, J = 8.4 Hz, 1H), 7.31-7.19(m, 4H), 7.06 (d, J = 8.8 Hz, 2H), 4.83-4.78 (m, 1H), 4.57-4.29 (m, 3H),3.80-3.69 (m, 6H), 3.25-2.90 (m, 4H), 2.51-2.23 (m, 4H), 1.76-1.71 (m,1H), 1.17 (d, J = 6.8 Hz, 3H) 95

459 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.33 (d, J = 2 Hz, 2H), 7.32-7.24(m, 3H), 7.14 (d, J = 8.8 Hz, 2H), 4.83- 4.68 (m, 2H), 4.37 (d, J = 6Hz, 2H), 3.82 (s, 3H), 3.30-3.03 (m, 2H), 2.81- 2.53 (m, 6H), 2.30-2.01(m, 3H), 1.82-1.53 (m, 6H), 1.20 (d, J = 8.8 Hz, 3H) 96

459 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.36 (d, J = 8.9 Hz, 1H), 7.30-7.28(m, 1H), 7.27-7.26 (m, 1H), 7.25- 7.17 (m, 3H), 7.06 (d, J = 8.9 Hz,1H), 4.81-4.79 (m, 1H), 4.41-4.27 (m, 2H), 4.10-3.92 (m, 1H), 3.78 (s,3H), 3.55 (s, 2H), 3.37 (s, 2H), 3.35-3.19 (m, 1H), 3.12-2.96 (m, 1H),2.35-2.19 (m, 1H), 2.19-1.93 (m, 4H), 1.83-1.67 (m, 1H), 1.53- 1.42 (m,1H), 1.39-1.20 (m, 3H), 1.17 (d, J = 6.7 Hz, 3H) 97

405 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.40 (d, J = 8.7 Hz, 1H), 7.31-7.11(m, 6H), 4.82-4.76 (m, 1H), 4.36 (d, J = 6.0 Hz, 2H), 4.20 (d, J = 7.2Hz, 2H), 3.77 (s, 3H), 3.61-3.53 (m, 2H), 3.34-3.21 (m, 3H), 3.07-2.92(m, 2H), 2.28-2.20 (m, 1H), 1.78-1.70 (m, 1H), 1.17 (d, J = 6.9 Hz, 3H)98

445 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.47-7.40 (m, 1H), 7.37-7.32 (m,1H), 7.30-7.27 (m, 1H), 7.26-7.24 (m, 2H), 7.17-7.15 (m, 2H), 4.84- 4.78(m, 1H), 4.50-4.44 (m, 1H), 4.39-4.32 (m, 2H), 3.80 (s, 3H), 3.30-3.20(m, 3H), 3.15-3.01 (m, 3H), 2.75-2.70 (m, 2H), 2.32-2.12 (m, 3H),1.92-1.90 (m, 1H), 1.80- 1.72 (m, 2H), 1.20 (d, J = 6.6 Hz, 3H) 99

489 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.43 (d, J = 8.8 Hz, 1H), 7.26-7.13(m, 2H), 6.77-6.73 (m, 1H), 6.63- 6.60 (m, 2H), 4.83-4.77 (m, 1H),4.61-4.45 (m, 2H), 4.34-4.22 (m, 2H), 3.95 (d, J = 15.4 Hz, 4H), 3.79(s, 3H), 3.30-3.19 (m, 1H), 3.07- 2.97 (m, 3H), 2.59-2.49 (m, 2H),2.31-2.20 (m, 1H), 1.79-1.69 (m, 1H), 1.29-1.24 (m, 6H), 1.17 (d, J =6.6 Hz, 3H) 100

475 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.40-7.28 (m, 1H), 7.24-7.21 (m,2H), 6.81-6.73 (m, 3H), 4.83-4.78 (m, 1H), 4.59-4.54 (m, 1H), 3.81- 3.76(m, 9H), 3.25-3.19 (m, 5H), 3.17-2.95 (m, 3H), 2.69-2.58 (m, 3H),2.31-2.23 (m, 1H), 1.77-1.71 (m, 1H), 1.18 (d, J = 6.9 Hz, 3H) 101

503 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.39 (d, J = 8.9 Hz, 1H), 7.26-7.16(m, 2H), 6.77-6.69 (m, 3H), 4.80- 4.78 (m, 1H), 4.57-4.43 (m, 2H),3.85-3.83 (m, 3H), 3.79 (s, 3H), 3.23-2.95 (m, 9H), 2.66-2.60 (m, 2H),2.26-2.24 (m, 1H), 1.75-1.71 (m, 1H), 1.30-1.25 (m, 6H), 1.16 (d, J =6.7 Hz, 3H) 102

437 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.57 (d, J = 9.0 Hz, 1H), 7.48-7.29(m, 2H), 7.14-6.95 (m, 3H), 4.85-4.73 (m, 1H), 4.49-4.29 (m, 3H), 3.80(s, 3H), 3.33-2.91 (m, 4H), 2.62-2.54 (m, 2H), 2.47-2.19 (m, 3H),1.87-1.70 (m, 1H), 1.50-1.42 (m, 2H), 1.17 (d, J = 6.6 Hz, 3H) 103

467 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.52-7.41 (m, 2H), 6.94-6.85 (m,3H), 4.83-4.77 (m, 1H), 4.35-4.23 (m, 3H), 3.85 (s, 3H), 3.79 (s, 3H),3.39 (d, J = 10.6 Hz, 2H), 3.34-3.16 (m, 1H), 3.11-2.95 (m, 1H),2.78-2.65 (m, 4H), 2.30-2.23 (m, 1H), 1.79-1.72 (m, 1H), 1.66-1.51 (m,2H), 1.18 (d, J = 6.7 Hz, 3H) 104

433 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.52 (d, J = 9.0 Hz, 1H), 7.41-7.13(m, 6H), 4.86-4.69 (m, 1H), 4.30- 4.18 (m, 1H), 3.79 (s, 3H), 3.33-3.07(m, 7H), 2.98-2.88 (m, 1H), 2.76- 2.57 (m, 2H), 2.44-2.18 (m, 3H),1.83-1.67 (m, 1H), 1.51-1.29 (m, 2H), 1.16 (d, J = 6.7 Hz, 3H) 105

473 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.38-7.36 (m, 1H), 7.32-7.30 (m,2H), 7.25-7.21 (m, 4H), 4.77-4.43 (m, 1H), 4.39-4.38 (m, 2H), 4.21-4.15(m, 1H), 3.76 (s, 3H), 3.24-3.16 (m, 3H), 3.03- 2.99 (m, 2H), 2.97-2.91(m, 1H), 2.37 (s, 3H), 2.27-2.20 (m, 1H), 2.11-2.01 (m, 2H), 1.97-1.94(m, 2H), 1.78-1.72 (m, 1H), 1.44-1.37 (m, 4H), 1.14 (d, J = 5.1 Hz, 3H)106

449 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.63 (d, J = 9.1 Hz, 1H), 7.39-7.17(m, 6H), 4.80-4.68 (m, 1H), 4.42 (s, 3H), 3.75 (s, 3H), 3.27-3.13 (m,1H), 3.12-2.99 (m, 2H), 2.98-2.83 (m, 4H), 2.82-2.68 (m, 1H), 2.65 (s,1H), 2.60- 2.34 (m, 2H), 2.32-2.14 (m, 1H), 1.82-1.65 (m, 1H), 1.36 (d,J = 12.4 Hz, 1H), 1.10 (d, J = 6.6 Hz, 3H) 107

449 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.54-7.52 (d, J = 8.0 Hz, 1H),7.41- 7.39 (d, J = 8.8 Hz, 1H), 7.20-7.18 (d, J = 8.4 Hz, 2H), 6.91-6.89(d, J = 8.8 Hz, 2H), 4.81-4.76 (m, 1H), 4.40- 4.36 (m, 3H), 3.79-3.77(m, 6H), 3.34-3.21 (m, 1H), 3.21-3.02 (m, 2H), 3.00-2.96 (m, 1H),2.58-2.57 (m, 2H), 2.37-2.25 (m, 3H), 1.80-1.75 (m, 1H), 1.48-1.40 (m,2H), 1.17-1.16 (d, J = 6.4 Hz, 3H) 108

489 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.41-7.38 (d, J = 9 Hz, 1H),7.30-7.16 (m, 3H), 6.92-6.88 (m, 2H), 4.81-4.75 (m, 1H), 4.33 (s, 2H),4.28-4.20 (m, 1H), 3.79-3.73 (m, 6H), 3.63 (s, 2H), 3.42 (s, 2H),3.28-3.17 (m, 1H), 3.02- 2.92 (m, 1H), 2.33-2.24 (m, 1H), 2.16-2.09 (m,4H), 1.82-1.74 (m, 1H), 1.51-1.42 (m, 4H), 1.15-1.13 (d, J = 6.6 Hz, 3H)109

463 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52-7.48 (m, 2H), 7.37-7.34 (m,1H), 7.26-7.24 (m, 1H), 6.21-6.20 (m, 1H), 4.76-4.73 (m, 1H), 4.65-4.62(m, 2H), 4.25-4.16 (m, 1H), 3.87-3.85 (m, 2H), 3.75 (s, 3H), 3.63-3.57(m, 2H), 3.51- 3.47 (m, 2H), 3.15-3.11 (m, 1H), 2.93-2.89 (m, 1H),2.25-2.13 (m, 5H), 1.74-1.57 (m, 5H), 1.12 (d, J = 6.8 Hz, 3H) 110

461 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.44-7.40 (m, 2H), 7.26-7.22 (m,1H), 6.84-6.69 (m, 3H), 4.90-4.76 (m, 2H), 4.36 (s, 2H), 3.93-3.91 (m,1H), 3.80- 3.76 (m, 9H), 3.23-3.21 (m, 1H), 3.19-2.93 (m, 3H), 2.54-2.24(m, 3H), 1.81-1.74 (m, 1H), 1.16 (d, J = 6.8 Hz, 3H)

Examples 111 and 112: methyl(S)-2-benzyl-7-methyl-3-((S)-7-azaspiro[3.5]nonan-1-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-2-benzyl-7-methyl-3-((R)-7-azaspiro[3.5]nonan-1-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(2S)-5-amino-6-([7-[(tert-butoxy)carbonyl]-7-azaspiro[3.5]nonan-1-yl]amino)-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 10-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(100 mg, 0.33 mmol, Intermediate 1) was dissolved in toluene (4 mL).Then tert-butyl 1-amino-7-azaspiro[3.5]nonane-7-carboxylate (242 mg,1.01 mmol), Brettphos (36 mg, 0.07 mmol), 3^(rd) Generation BrettPhosprecatalyst (60.8 mg, 0.07 mmol) and sodium tert-butoxide (48.3 mg, 0.50mmol) were added. The resulting solution was stirred for 1 h at 100° C.under nitrogen atmosphere. The reaction mixture was cooled to roomtemperature and the solids were filtered out. The filtrate wasconcentrated under vacuum. The residue was subjected to purification byFCC eluting with ethyl acetate/petroleum ether (2:1). This afforded thetitle compound (52.8 mg, 34%) as a brown solid. MS: (ES, m/z): 459[M+H]⁺.

Step 2. Synthesis of tert-butyl1-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-7-azaspiro[3.5]nonane-7-carboxylate

Into a 25-mL round-bottom flask, methyl(2S)-5-amino-6-([7-[(tert-butoxy)carbonyl]-7-azaspiro[3.5]nonan-1-yl]amino)-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(52.8 mg, 0.12 mmol) was dissolved in dichloromethane (5 mL). Then2-phenylacetaldehyde (83 mg, 0.69 mmol) was added. The resultingsolution was stirred for 4 h at room temperature. The resulting mixturewas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (2:1). This affordedthe title compound (25 mg, 39%) as a yellow oil. MS: (ES, m/z): 559[M+H]⁺.

Step 3. Synthesis of methyl(S)-2-benzyl-7-methyl-3-((S)-7-azaspiro[3.5]nonan-1-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-2-benzyl-7-methyl-3-((R)-7-azaspiro[3.5]nonan-1-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, tert-butyl1-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]-7-azaspiro[3.5]nonane-7-carboxylate(25 mg, 0.04 mmol) was dissolved in dichloromethane (5 mL). Thentrifluoroacetic acid (1 mL) was added. The resulting solution wasstirred for 2 h at room temperature. The resulting mixture wasconcentrated under vacuum. The crude product was purified by Prep-HPLCwith the following conditions: Column, XBridge C18 OBD Prep Column, 100Å, 5 um, 19 mm×250 mm; mobile phase, A: Water (containing 10 mmol/LNH₄HCO₃) and B: ACN (25.0% to 40.0% ACN over 8 min); UV Detector: 254nm. This afforded the title compounds as follows: 2.4 mg (12%) of methyl(7S)-3-[(1R)-7-azaspiro[3.5]nonan-1-yl]-2-benzyl-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, first eluting isomer, RT=5.8 min) as a whitesolid and 1.7 mg (8%) of methyl(7S)-3-[(1S)-7-azaspiro[3.5]nonan-1-yl]-2-benzyl-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, second eluting isomer, RT=7.1 min) as a whitesolid.

First eluting isomer: ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.69 (d, J=9.0Hz, 1H), 7.48 (d, J=9.0 Hz, 1H), 7.39-7.23 (m, 3H), 7.21-7.14 (m, 2H),4.82-4.78 (m, 1H), 4.68-4.62 (m, 1H), 4.50-4.32 (m, 2H), 3.80 (s, 3H),3.28-3.06 (m, 2H), 3.02-2.96 (m, 1H), 2.88-2.81 (m, 1H), 2.77-2.55 (m,3H), 2.40-2.15 (m, 3H), 1.89-1.66 (m, 4H), 1.48-1.40 (m, 1H), 1.18 (d,J=6.7 Hz, 3H), 1.09-1.02 (m, 1H). MS: (ES, m/z): 459 [M+H]⁺.

Second eluting isomer: ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.70 (d, J=9.0Hz, 1H), 7.48 (d, J=9.0 Hz, 1H), 7.39-7.23 (m, 3H), 7.22-7.15 (m, 2H),4.82-4.77 (m, 1H), 4.72-4.68 (m, 1H), 4.48-4.32 (m, 2H), 3.81 (s, 3H),3.25-3.08 (m, 2H), 3.02-2.94 (m, 1H), 2.90-2.82 (m, 1H), 2.80-2.60 (m,3H), 2.42-2.30 (m, 1H), 2.28-2.16 (m, 2H), 1.94-1.88 (m, 1H), 1.87-1.67(m, 3H), 1.45-1.38 (m, 1H), 1.17 (d, J=6.7 Hz, 3H), 1.12-1.08 (m, 1H).MS: (ES, m/z): 459 [M+H]⁺.

The following examples in TABLE 7 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Examples 111 and 112.

TABLE 7 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 113 and 114

1^(st) eluting isomer = 447 2^(nd) eluting isomer = 447 1^(st) elutingisomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.41-7.12 (m, 7H), 4.82-4.75 (m,1H), 4.39-4.37 (m, 1H), 4.07-4.03 (m, 1H), 3.98- 3.85 (m, 1H), 3.78 (s,3H), 3.34- 3.26 (m, 2H), 3.07-2.92 (m, 2H), 2.75-2.01 (m, 4H), 1.98-1.95(m, 1H), 1.85-1.73 (m, 1H), 1.55-1.42 (m, 4H), 1.17 (d, J = 6.6 Hz, 3H),1.12-0.88 (m, 2H) 2^(nd) eluting isomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm):7.37 (d, J = 8.4 Hz, 1H), 7 28-7.26 (m, 1H), 7.24- 7.17 (m, 5H),4.81-4.75 (m, 1H), 4.44-4.41 (m, 1H), 4.21-4.12 (m, 1H), 4.01-3.88 (m,1H), 3.78 (s, 3H), 3.56-3.27 (m, 2H), 3.06-2.99 (m, 2H), 2.72-2.06 (m,5H), 1.99- 1.96 (m, 2H), 1.48-1.29 (m, 3H), 120 (d, J = 6.6 Hz, 3H),1.11-0.85 (m, 2H) 115, 116, 117 and 118

1^(st) eluting isomer = 447 2^(nd) eluting isomer = 447 3^(rd) elutingisomer = 447 4^(th) eluting isomer = 447 1^(st) eluting isomer ¹H-NMR(CDCl₃, 300 MHz) δ (ppm): 9.42 (s, 1H), 7.74 (d, J = 8.9 Hz, 1H),7.57-7.51 (m, 1H), 7.52-7.23 (m, 5H), 4.94 (s, 1H), 4.93-4.74 (m, 2H),4.45 (s, 1H), 3.81 (s, 3H), 3.35-2.90 (m, 4H), 2.66 (s, 3H), 2.02-1.53(m, 3H), 1.44 (s, 2H), 1.21 (s, 3H), 1.14 (d, J = 6.6 Hz, 3H) 2^(nd)eluting isomer ¹H-NMR (CD₃, 300 MHz) δ (ppm): 7.38 (d, J = 8.8 Hz, 1H),7.33-7.28 (m, 2H), 7.26-7.20 (m, 4H), 4.82-4.80 (m, 1H), 4.40-4.22 (m,2H), 4.10-3.98 (m, 1H), 3.78 (s, 3H), 3.35-3.17 (m, 1H), 3.14-2.98 (m,1H), 2.89 (d, J = 12.0 Hz, 1H), 2.48-2.37 (m, 2H), 2.34-2.16 (m, 2H),2.00 (d, J = 13.1 Hz, 1H), 1.82-1.71 (m, 3H), 1.44 (s, 1H), 1.26 (d, J =6.9 Hz, 3H), 1.19 (d, J = 6.7 Hz, 3H), 1.09-0.85 (m, 1H) 3^(rd) elutingisomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.42 (d, J = 8.9 Hz, 1H),7.32-7.27 (m, 2H), 7.26-7.20 (m, 4H), 4.83-4.79 (m, 1H), 4.32 (s, 2H),4.05-3.91 (m, 1H), 3.80 (s, 3H), 3.41-3.19 (m, 2H), 3.16-2.98 (m, 2H),2.53-2.17 (m, 4H), 1.81-1.74 (m, 1H), 1.50- 1.38 (m, 2H), 1.29 (d, J =6.9 Hz, 3H), 1.18 (d, J = 6.7 Hz, 3H), 1.15-1.04 (m, 1H), 0.38-0.25 (m,1H) 4^(th) eluting isomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.42 (d, J =8.9 Hz, 1H), 7.33-7.27 (m, 2H), 7.25-7.19 (m, 4H), 4.82-4.78 (m, 1H),4.41-4.22 (m, 2H), 4.06-3.93 (m, 1H), 3.79 (s, 3H), 3.54 (d, J = 11.4Hz, 1H), 3.39-3.17 (m, 2H), 3.14-2.98 (m, 1H), 2.81-2.53 (m, 2H), 2.44(t, J = 11.9 Hz, 1H), 2.35-2.17 (m, 1H), 1.85-1.68 (m, 1H), 1.64 (s,2H), 1.28-1.22 (m, 3H), 1.25-1.16 (m, 4H), 0.50 (s, 1H) 119, 120, 121and 122

1^(st) eluting isomer = 433 2^(nd) eluting isomer = 433 3^(rd) elutingisomer = 433 4^(th) eluting isomer = 433 1^(st) eluting isomer ¹H-NMR(CDCl₃, 400 MHz) δ (ppm): 7.46-7.34 (m, 2H), 7.33-7.27 (m, 2H),7.26-7.17 (m, 3H), 4.85-4.76 (m, 1H), 4.52- 4.38 (m, 1H), 4.36-1.21 (m,1H), 3.85-3.65 (m, 4H), 3.34-3.18 (m, 2H), 3.18-3.01 (m, 2H), 2.64-2.53(m, 1H), 2.51-2.40 (m, 1H), 2.36- 2.16 (m, 3H), 1.82-1.71 (m, 1H),1.30-1.22 (m, 1H), 1.15-1.20 (m, 3H), 1.06-0.80 (m, 1H), 0.45-0.34 (m,3H) 2^(nd) eluting isomer ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.56-7.52 (m,2H), 7.39-7.26 (m, 2H), 7.25-7.20 (m, 3H), 4.85-4.75 (m, 1H), 4.58- 4.48(m, 1H), 4.27-4.17 (m, 1H), 3.85-3.72 (m, 4H), 3.34-3.21 (m, 2H),3.18-3.01 (m, 2H), 2.66-2.52 (m, 1H), 2.45-2.22 (m, 4H), 1.82- 1.71 (m,1H), 1.39-1.00 (m, 5H), 0.62-0.48 (m, 3H) 3^(rd) eluting isomer ¹H-NMR(CDCl₃, 400 MHz) δ (ppm): 7.46-7.26 (m, 4H), 7.25-7.16 (m, 3H),4.86-4.75 (m, 1H), 4.47-4.25 (m, 3H), 3.78 (s, 3H), 3.41-3.20 (m, 2H),3.12- 3.01 (m, 1H), 2.93-2.73 (m, 3H), 2.60 (t, J = 12.0 Hz, 1H), 2.32-2.19 (m, 1H), 1.82-1.72 (m, 1H), 1.69-1.50 (m, 2H), 1.37-1.26 (m, 1H),1.17 (d, J = 6.8 Hz, 3H), 1.11 (d, J = 7.2 Hz, 3H) 4^(th) eluting isomer¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.44-7.17 (m, 7H), 4.88-4.79 (m, 1H),4.50-1.31 (m, 3H), 3.81 (s, 3H), 3.36-3.20 (m, 2H), 3.19-3.02 (m, 1H),2.97- 2.70 (m, 3H), 2.58-2.42 (m, 1H), 2.36-2.17 (m, 1H), 1.87-1.78 (m,3H), 1.59-1.49 (m, 1H), 1.18 (d, J = 6.8 Hz, 3H), 1.11 (d, J = 7.2 Hz,3H). 123, 124, 125 and 126

1^(st) eluting isomer = 433 2^(nd) eluting isomer = 433 3^(rd) elutingisomer = 433 4^(th) eluting isomer = 433 1^(st) eluting isomer ¹H-NMR(CD₃OD, 300 MHz) δ (ppm): 7.55 (d, J = 9.0 Hz, 1H), 7.46-7.20 (m, 6H),4.82-4.72 (m, 1H), 4.65-4.42 (m, 3H), 3.80 (s, 3H), 3.30-3.18 (m, 1H),3.02-2.82 (m, 3H), 2.58- 2.48 (m, 1H), 2.40-2.20 (m, 2H), 1.82-1.74 (m,1H), 1.62-1.52 (m, 1H), 1.32-1.13 (m, 5H), 1.00 (d, J = 7.1 Hz, 3H)2^(nd) eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.55 (d, J = 9.0Hz, 1H), 7.46-7.20 (m, 6H), 4.82-4.72 (m, 1H), 4.65-4.42 (m, 3H), 3.80(s, 3H), 3.30-3.18 (m, 1H), 3.02-2.82 (m, 3H), 2.52- 2.22 (m, 3H),1.82-1.74 (m, 1H), 1.62-1.52 (m, 1H), 1.32-1.13 (m, 5H), 1.00 (d, J =7.1 Hz, 3H) 3^(rd) eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.55(d, J = 9.0 Hz, 1H), 7.46-7.20 (m, 6H), 4.82-4.72 (m, 1H), 4.65-4.42 (m,3H), 3.80 (s, 3H), 3.30-3.18 (m, 1H), 3.02-2.92 (m, 2H), 2.64- 2.52 (m,2H), 2.32-2.12 (m, 2H), 2.00-1.72 (m, 2H), 1.45-1.30 (m, 2H), 1.26-1.13(m, 3H), 1.08 (d, J = 6.3 Hz, 3H) 4^(th) eluting isomer ¹H-NMR (CD₃OD,300 MHz) δ (ppm): 7.55 (d, J = 9.0 Hz, 1H), 7.46-7.20 (m, 6H), 4.82-4.72(m, 1H), 4.65-4.42 (m, 3H), 3.80 (s, 3H), 3.30-3.18 (m, 1H), 3.02-2.92(m, 2H), 2.64- 2.52 (m, 2H), 2.32-2.12 (m, 2H), 2.00-1.72 (m, 2H),1.45-1.30 (m, 2H), 1.26-1.13 (m, 3H), 1.08 (d, J = 6.3 Hz, 3H) 127 and128

1^(st) eluting isomer = 445 2^(nd) eluting isomer = 445 1st elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58- 7.45 (m, 2H), 7.38-7.15(m, 5H), 5.03-4.89 (m, 1H), 4.84-4.74 (m, 1H), 4.43 (s, 2H), 3.80 (s,3H), 3.29-3.12 (m, 5H), 3.02-2.92 (m, 3H), 2.39-2.21 (m, 3H), 2.17-2.12(m, 2H), 1.79-1.72 (m, 1H), 1.17 (d, J = 6.6 Hz, 3H) 2^(nd) elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55- 7.44 (m, 2H), 7.38-7.15(m, 5H), 5.02-4.92 (m, 1H), 4.82-4.78 (m, 1H), 4.43 (s, 2H), 3.80 (s,3H), 3.30-3.15 (m, 5H), 3.04-2.88 (m, 3H), 2.34-2.17 (m, 3H), 2.08-2.02(m, 2H), 1.79-1.72 (m, 1H), 1.17 (d, J = 6.6 Hz, 3H) 129, 130, 131 and132

1^(st) eluting isomer = 445 2^(nd) eluting isomer = 445 3^(rd) elutingisomer = 445 4^(th) eluting isomer = 445 1st eluting isomer ¹H-NMR(CD₃OD, 300 MHz) δ (ppm): 7.50- 7.19 (m, 7H), 4.81-4.77 (m, 1H),4.53-4.33 (m, 3H), 3.80 (s, 3H), 3.29-3.12 (m, 3H), 3.08-2.93 (m, 2H),2.80-2.72 (m, 2H), 2.45-2.00 (m, 5H), 1.82-1.72 (m, 2H), 1.18 (d, J =3.0 Hz, 1H) 2nd eluting isomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.30-7.10 (m, 7H), 4.69-4.62 (m, 1H), 4.35-4.20 (m, 3H), 3.68 (s, 3H),3.52-3.48 (m, 2H), 3.15-3.02 (m, 2H), 2.92-2.84 (m, 2H), 2.65-2.60 (m,1H), 2.30-1.92 (m, 5H), 1.70- 1.60 (m, 2H), 1.05 (d, J = 4.0 Hz, 3H) 3rdeluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.62 (d, J = 9.1 Hz,1H), 7.50-7.17 (m, 6H), 4.86-4.75 (m, 1H), 4.48-4.46 (m, 2H), 3.80 (s,3H), 3.28-2.78 (m, 5H), 2.69-2.52 (m, 3H), 2.50- 2.38 (m, 2H), 2.30-2.22(m, 1H), 2.00-1.90 (m, 1H), 1.85-1.69 (m, 3H), 1.19 (d, J = 6.6 Hz, 3H)4^(th) eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.65- 7.18 (m,7H), 4.85-4.78 (m, 2H), 4.48-4.46 (m, 2H), 3.79 (s, 3H), 3.27-3.15 (m,2H), 3.10-2.60 (m, 5H), 2.48-2.40 (m, 2H), 2.32-2.20 (m, 1H), 2.04-1.92(m, 1H), 1.86- 1.68 (m, 3H), 1.15 (d, J = 4.50 Hz, 3H)

Examples 133 and 134:(2R)-3-[(7S)-6-(methoxycarbonyl)-3,7-dimethyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-2-yl]-2-phenylpropanoicacid and(2S)-3-[(7S)-6-(methoxycarbonyl)-3,7-dimethyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-2-yl]-2-phenylpropanoicacid

Step 1. Synthesis of methyl(S)-5-amino-6-(benzylamino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 50-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(250 mg, 1.66 mmol, Intermediate 1) was dissolved in toluene (20 mL).Then benzyl amine (375 mg, 3.5 mmol), Brettphos (144 mg, 0.26 mmol),3^(rd) Generation BrettPhos precatalyst (122 mg, 0.14 mmol) and sodiumtert-butoxide (483 mg, 5.0 mmol) were added. The resulting solution wasstirred for 1 h at 110° C. under nitrogen atmosphere. The reactionmixture was cooled to room temperature and the solids were filtered out.The filtrate was concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (2:1).This afforded the title compound (352 mg, 65%) as a yellow solid. MS:(ES, m/z): 325 [M+H]⁺.

Step 2. Synthesis of methyl(7S)-3-benzyl-2-(3-ethoxy-3-oxo-2-phenylpropyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-(benzylamino)-2-methyl-1,2,3,4-tetrahydronaphthalene-1-carboxylate(350 mg, 0.86 mmol) was dissolved in dichloromethane (10 mL). Then ethyl4-oxo-2-phenylbutanoate (281 mg, 1.29 mmol, Intermediate 32) was added.The resulting solution was stirred for 2 h at room temperature. Theresulting mixture was concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (1:2). This afforded the title compound (210 mg, 48%) as a yellowsolid. MS: (ES, m/z): 512 [M+H]⁺.

Step 3. Synthesis of methyl(7S)-2-(3-ethoxy-3-oxo-2-phenylpropyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(7S)-3-benzyl-2-(3-ethoxy-3-oxo-2-phenylpropyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(100 mg, 0.19 mmol) was dissolved in methanol (5 mL). Then palladium oncarbon (10%, 50 mg) was added and hydrogen (g) was charged into thereaction mixture. The reaction mixture was stirred overnight at roomtemperature. The reaction was vented to nitrogen and the solids werefiltered out over celite. The filtrate was concentrated under vacuum.This afforded the title compound (80 mg, 98%) as a yellow oil. MS: (ES,m/z): 422 [M+H]⁺.

Step 4. Synthesis of methyl(7S)-2-[(2R)-3-ethoxy-3-oxo-2-phenylpropyl]-3,7-dimethyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(7S)-2-[(2S)-3-ethoxy-3-oxo-2-phenylpropyl]-3,7-dimethyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(7S)-2-(3-ethoxy-3-oxo-2-phenylpropyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(70 mg, 0.16 mmol) was dissolved in N,N-dimethylformamide (2 mL) andthen cesium carbonate (107 mg, 0.32 mmol) were added. This was followedby the addition of methyl iodide (22.8 mg, 0.16 mmol) dropwise withstirring. The resulting solution was stirred for 1 h at rt (20° C.). Theresulting solution was diluted with 20 mL of water and extracted with3×20 mL of ethyl acetate. The organic layers were combined, dried overanhydrous sodium sulfate, filtered and concentrated under vacuum. Theresidue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:1). The crude product was purified byChiral-Prep-HPLC with the following conditions (Prep-HPLC): Column, (R,R) WHELK-01 5/100 Kromasil, 25 cm×21.1 mm; mobile phase: A: Hex (0.1%DEA) and B: ethanol (hold 30.0% ethanol in 38 min); UV Detector: 254 nm.This afforded the title compounds as follows: 30 mg (43%) of methyl(7S)-2-[(2R)-3-ethoxy-3-oxo-2-phenylpropyl]-3,7-dimethyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateas a yellow oil (assumed stereochemistry, first eluting isomer) and 30mg (43%) of(7S)-2-[(2S)-3-ethoxy-3-oxo-2-phenylpropyl]-3,7-dimethyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, first eluting isomer) as a yellow oil. MS:(ES, m/z): 436 [M+H]⁺.

Step 5A. Synthesis of(2R)-3-[(7S)-6-(methoxycarbonyl)-3,7-dimethyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-2-yl]-2-phenylpropanoicacid

Into a 50-mL round-bottom flask, methyl(7S)-2-[(2R)-3-ethoxy-3-oxo-2-phenylpropyl]-3,7-dimethyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(30 mg, 0.07 mmol) was dissolved in tetrahydrofuran (2 mL). Then asolution of lithium hydroxide (8.2 mg, 0.34 mmol) in water (2 mL) wasadded. The resulting solution was stirred overnight at 85° C. in an oilbath. The reaction mixture was cooled to room temperature and the solidswere filtered out. The crude product was purified by Prep-HPLC with thefollowing conditions: Column, XBridge Prep C18 OBD Column, 5 μm, 19×150mm; mobile phase: A: water (containing 0.05% TFA) and B: ACN (25.0% toACN 45.0% over 7 min); UV Detector: 254 nm. This afforded the titlecompound (3.9 mg, 14%) as a white solid.

1H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.85-7.90 (m, 1H), 7.33-7.22 (m, 4H),7.20-7.16 (m, 2H), 4.84-4.80 (m, 1H), 4.67-4.63 (m, 1H), 3.88 (s, 3H),3.68 (s, 3H), 3.56-3.49 (m, 1H), 3.21-3.16 (m, 2H), 3.03-2.94 (m, 1H),2.17-2.11 (m, 1H), 1.84-1.79 (m, 1H), 1.12 (d, J=6.8 Hz, 3H). MS: (ES,m/z): 408 [M+H]⁺.

Step 5B. Synthesis of(2S)-3-[(7S)-6-(methoxycarbonyl)-3,7-dimethyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-2-yl]-2-phenylpropanoicacid

Into a 50-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(7S)-2-[(2S)-3-ethoxy-3-oxo-2-phenylpropyl]-3,7-dimethyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(30 mg, 0.07 mmol) was dissolved in tetrahydrofuran (2 mL), and then asolution of lithium hydroxide (8.2 mg, 0.34 mmol) in water (2 mL) wasadded. The resulting solution was stirred overnight at 85° C. in an oilbath. The reaction mixture was cooled to rt (20° C.). The solids werefiltered out. The crude product was purified by Prep-HPLC with thefollowing conditions: Column, XBridge Prep C18 OBD Column, 5 um, 19×150mm; mobile phase: A: Water (containing 0.05% TFA) and B: ACN (25.0% ACNup to 45.0% in 7 min); UV Detector: 254/220 nm. This afforded the titlecompound (3.8 mg, 14%) as a white solid. 1H-NMR (CDCl₃, 400 MHz) δ(ppm): 7.88-7.92 (m, 1H), 7.52-7.33 (m, 5H), 7.28-7.25 (m, 1H),4.90-4.81 (m, 2H), 4.00-3.93 (m, 1H), 3.86-3.63 (m, 6H), 3.34-3.26 (m,1H), 3.12-3.05 (m, 2H), 2.13-2.10 (m, 1H), 1.80-1.73 (m, 1H), 1.12-1.05(m, 3H). MS: (ES, m/z): 408 [M+H]⁺.

Examples 135 and 136:(S)-3-((S)-6-(methoxycarbonyl)-3,7-dimethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid and(R)-3-((S)-6-(methoxycarbonyl)-3,7-dimethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid

Step 1. Synthesis of methyl(S)-5,6-diamino-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 50-mL round-bottom flask, methyl(S)-5-amino-6-(benzylamino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate(160 mg, 0.49 mmol) was dissolved in methanol (25 mL). Then 10%palladium on carbon (20 mg) was added. Hydrogen (g) was charged into thereaction mixture and the reaction was stirred under a hydrogenatmosphere for 3 h at room temperature. The solids were filtered outover celite and the filtered solution was concentrated under vacuumaffording the title compound (112 mg, 97%) as a yellow oil. MS: (ES,m/z): 236 [M+H]⁺.

Step 2. Synthesis ofmethyl-(2S)-5-amino-6-(4-methoxy-4-oxo-3-phenylbutanamido)-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 50-mL round-bottom flask,methyl-(2S)-5,6-diamino-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(110 mg, 0.47 mmol) was dissolved in N,N-dimethylformamide (3 mL). Then4-methoxy-4-oxo-3-phenylbutanoic acid (97 mg, 0.47 mmol),diisopropylethylamine (182 mg, 1.41 mmol) andO-(7-azabenzotriazole-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (268 mg, 0.70 mmol) were added, successively. Theresulting solution was stirred for 1 h at room temperature. Theresulting solution was diluted with 20 mL of water and extracted with3×30 mL of ethyl acetate. The organic layers were combined, dried overanhydrous sodium sulfate, filtered and concentrated under vacuum. Thisafforded the title compound (40 mg, 20%) as a light yellow oil. MS: (ES,m/z): 426 [M+H]⁺

Step 3. Synthesis ofmethyl-(7S)-2-(3-methoxy-3-oxo-2-phenylpropyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask,methyl-(2S)-5-amino-6-(4-methoxy-4-oxo-3-phenylbutanamido)-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(40 mg, 0.09 mmol) was dissolved in dimethyl sulfoxide (2 mL). Thenacetic acid (2 mL) and sulfuric acid (0.01 mL) were added. The resultingsolution was stirred for 2 h at 60° C. The resulting solution was cooledto room temperature and diluted with 50 mL of water. The mixture wasextracted with 3×50 mL of ethyl acetate. The organic layers werecombined, dried over anhydrous sodium sulfate, filtered and concentratedunder vacuum. This afforded the title compound (20 mg, 52%) as a lightyellow oil. MS: (ES, m/z): 408 [M+H]⁺

Step 4. Synthesis of(S)-3-((S)-6-(methoxycarbonyl)-3,7-dimethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid and(R)-3-((S)-6-(methoxycarbonyl)-3,7-dimethyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid

Into a 50-mL round-bottom flask,methyl-(7S)-2-(3-methoxy-3-oxo-2-phenylpropyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(20 mg, 0.05 mmol) was dissolved in tetrahydrofuran (2 mL). Then water(2 mL) was added, followed by lithium hydroxide (7 mg, 0.29 mmol). Theresulting solution was stirred for 12 h at 85° C. The resulting mixturewas cooled to room temperature and concentrated under vacuum. The pHvalue of the solution was adjusted to 3 with hydrogen chloride (1mol/L). The resulting solution was extracted with 3×20 mL of ethylacetate. The organic layers were combined, dried over anhydrous sodiumsulfate, filtered and concentrated under vacuum. The crude product waspurified by Prep-HPLC with the following conditions: Column, XBridge C18OBD Prep Column, 100 Å, 5 m, 19 mm×250 mm; mobile phase, A: water(containing 0.05% TFA) and B: ACN (5.0% to 60% ACN over 30 min); UVDetector: 254 nm. Then the product was purified by Chiral-HPLC with thefollowing conditions: Column: (R,R)-WHELK-01-Kromasil, 5 cm×25 cm (5 m);Mobile Phase, A: Hexanes (containing 0.1% DEA) and B: EtOH (hold 40%EtOH in 38 min); UV Detector: 254 nm. This afforded the title compoundsas follows: 3.3 mg (17%) of3-[(7S)-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-2-yl]-2R-phenylpropanoicacid (assumed stereochemistry, first eluting isomer, RT=21.72) as awhite solid and 2.4 mg (12%) of3-[(7S)-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-2-yl]-2R-phenylpropanoicacid (assumed stereochemistry, second eluting isomer, RT=29.57) as whitesolid.

First eluting isomer: ¹H-NMR: (CD₃OD, 300 MHz) δ (ppm): 7.40-7.18 (m,7H), 4.80-4.75 (m, 1H), 4.15-4.10 (m, 1H), 3.77 (s, 3H), 3.61-3.58 (m,1H), 2.85-2.75 (m, 1H), 2.25-2.20 (m, 2H), 1.75-1.70 (m, 2H), 1.14-1.12(m, 3H). MS: (ES, m/z): 394 [M+H]⁺

Second eluting isomer: ¹H-NMR: (CD₃OD, 300 MHz) δ (ppm): 7.39-7.20 (m,7H), 4.80-4.75 (m, 1H), 4.15-4.10 (m, 1H), 3.77 (s, 3H), 3.65-3.60 (m,1H), 3.30-3.25 (m, 1H), 2.85-2.75 (m, 1H), 2.22-2.18 (m, 1H), 1.75-1.70(m, 2H), 1.13-1.11 (d, J=6.0 Hz, 3H). MS: (ES, m/z): 394 [M+H]⁺

Examples 137 and 138:(R)-3-((S)-3-(2-(dimethylamino)ethyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid and(S)-3-((S)-3-(2-(dimethylamino)ethyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid

Step 1. Synthesis of methyl (2S)-5-amino-6-[[2-(dimethylamino)ethyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 8-mL sealed tube purged and maintained with an inert atmosphereof nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(200 mg, 0.67 mmol, Intermediate 1) was dissolved in toluene (3 mL).Then (2-aminoethyl) dimethylamine (589.3 mg, 6.69 mmol), 3^(rd)Generation BrettPhos precatalyst (121.2 mg, 0.13 mmol), sodiumtert-butoxide (96.4 mg, 1.00 mmol) and Brettphos (143.5 mg, 0.27 mmol)were added. The resulting solution was stirred for 2 h at 110° C. undernitrogen atmosphere. The resulting mixture was cooled to roomtemperature and concentrated under vacuum. The crude product waspurified by Flash-Prep-HPLC with the following conditions: Column, C18silica gel; mobile phase, A: water (containing 0.5% TFA) and B: ACN(5.0% to 40.0% ACN over 30 min); UV Detector: 254 nm. This afforded thetitle compound (150 mg, 73%) as a yellow oil. MS: (ES, m/z): 307[M+H]⁺.

Step 2. Synthesis of methyl(7S)-3-[2-(dimethylamino)ethyl]-2-(3-ethoxy-3-oxo-2-phenylpropyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 8-mL sealed tube, methyl(2S)-5-amino-6-[[2-(dimethylamino)ethyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(150 mg, 0.47 mmol) was dissolved in dichloromethane (2 mL). Then ethyl4-oxo-2-phenylbutanoate (151.4 mg, 0.70 mmol, Intermediate 32) wasadded. The resulting solution was stirred for 2 h at room temperature.The resulting mixture was concentrated under vacuum. The crude productwas purified by Flash-Prep-HPLC with the following conditions: Column,C18 silica gel; mobile phase, A: water (containing 0.5% TFA) and B: ACN(5.0% to 60.0% ACN over 30 min); UV Detector: 254 nm. This afforded thetitle compound (150 mg, 65%) as yellow oil. MS: (ES, m/z): 493[M+H]⁺.

Step 3. Synthesis of(R)-3-((S)-3-(2-(dimethylamino)ethyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid and(S)-3-((S)-3-(2-(dimethylamino)ethyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid

Into a 50-mL round-bottom flask, methyl(7S)-3-[2-(dimethylamino)ethyl]-2-(3-ethoxy-3-oxo-2-phenylpropyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(130 mg, 0.25 mmol) was dissolved in tetrahydrofuran (2 mL). Then water(2 mL) was added, followed by lithium hydroxide (31.6 mg, 1.27 mmol).The resulting solution was stirred overnight at 85° C. The reactionmixture was cooled to room temperature. The resulting mixture wasconcentrated under vacuum. The crude product was purified by Prep-HPLCwith the following conditions: Column, XBridge Prep C18 OBD Column,19×150 mm, 5 μm; mobile phase: A: water (containing 0.05% TFA) and B:ACN (8.0% to 48.0% ACN over 12 min); UV Detector: 254 nm. The crudeproduct was purified by Chiral-Prep-HPLC with the following conditions:Column, (R, R)WHELK-01 5/100 Kromasil, 25 cm×21.1 mm; mobile phase: A:hexanes (containing 0.1% TFA) and B: ethanol (hold 30.0% ethanol in 38min); UV Detector: 254 nm. This afforded the title compounds as follows:15.1 mg (13%) of(2R)-3-[(7S)-3-[2-(dimethylamino)ethyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-2-yl]-2-phenylpropanoicacid (assumed stereochemistry, first eluting isomer, RT=18.6 min) as awhite solid and 17.8 mg (15%) of(2S)-3-[(7S)-3-[2-(dimethylamino)ethyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-2-yl]-2-phenylpropanoicacid (assumed stereochemistry, second eluting isomer, RT=26.4 min) as awhite solid.

First eluting isomer: ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.86-7.84 (m,1H), 7.63-7.59 (m, 1H), 7.28-7.19 (m, 5H), 4.91-4.65 (m, 4H), 3.84-3.78(m, 4H), 3.65-3.36 (m, 3H), 3.02-2.89 (m, 8H), 2.10-2.03 (m, 1H),1.77-1.70 (m, 1H), 1.12 (d, J=6.6 Hz, 3H). MS: (ES, m/z): 465[M+H]⁺.

Second eluting isomer: ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.86-7.83 (m,1H), 7.52-7.48 (m, 1H), 7.28-7.19 (m, 5H), 4.83-4.68 (m, 4H), 3.95-3.82(m, 4H), 3.50-3.45 (m, 2H), 3.14-3.08 (m, 1H), 2.98-2.96 (m, 2H),2.85-2.75 (m, 6H), 2.14-2.12 (m, 1H), 1.78-1.73 (m, 1H), 1.09 (d, J=6.9Hz, 3H). MS: (ES, m/z): 465[M+H]⁺.

Examples 139 and 140:(S)-3-((S)-6-(methoxycarbonyl)-7-methyl-3-(tetrahydro-2H-pyran-4-yl)-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid and(R)-3-((S)-6-(methoxycarbonyl)-7-methyl-3-(tetrahydro-2H-pyran-4-yl)-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid

Step 1. Synthesis ofmethyl-(2S)-5-amino-2-methyl-6-[(oxan-4-yl)amino]-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 50-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen,methyl-(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(150 mg, 0.50 mmol, Intermediate 1) was dissolved in toluene (5 mL).Then oxan-4-amine (150 mg, 1.48 mmol), Brettphos (54 mg, 0.10 mmol),3^(rd) Generation BrettPhos precatalyst (45 mg, 0.05 mmol) and sodiumtert-butoxide (100 mg, 1.04 mmol) were added successively. The resultingsolution was stirred for 2 h at 110° C. in the nitrogen atmosphere. Thereaction mixture was cooled and the resulting solids were filtered out.The filtrate was concentrated under vacuum. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (2:1).This afforded the title compound (110 mg, 69%) as a green oil. MS: (ES,m/z): 420[M+H]⁺

Step 2. Synthesis ofmethyl-(7S)-2-(3-methoxy-3-oxo-2-phenylpropyl)-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 100-mL round-bottom flask,methyl-(2S)-5-amino-2-methyl-6-[(oxan-4-yl)amino]-1,2,3,4-tetrahydroquinoline-1-carboxylate(160 mg, 0.50 mmol) was dissolved in dichloromethane (10 mL). Thenmethyl-4-oxo-2-phenylbutanoate (192 mg, 1.00 mmol, Intermediate 32) wasadded. The resulting solution was stirred for 12 h at room temperature.The resulting mixture was concentrated under vacuum. The residue wassubjected to purification by FCC with ethyl acetate/petroleum ether(2:1). This afforded the title compound (120 mg, 49%) as a yellow oil.MS: (ES, m/z): 492[M+H]⁺

Step 3. Synthesis of(S)-3-((S)-6-(methoxycarbonyl)-7-methyl-3-(tetrahydro-2H-pyran-4-yl)-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid and(R)-3-((S)-6-(methoxycarbonyl)-7-methyl-3-(tetrahydro-2H-pyran-4-yl)-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid

Into a 25-mL round-bottom flask,methyl-(7S)-2-(3-methoxy-3-oxo-2-phenylpropyl)-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(120 mg, 0.24 mmol) was dissolved in tetrahydrofuran (8 mL). Thenlithium hydroxide (31 mg, 1.29 mmol) dissolved in water (2 mL) was addeddropwise. The resulting solution was stirred for 12 h at 85° C. Aftercooled to room temperature, the resulting mixture was concentrated undervacuum. The product was purified with the following conditions: Column:XSelect CSH Prep C18 OBD Column, 19×250 mm, 5 um; Mobile Phases, A:Water (containing 0.05% TFA) and B: ACN (15% to 45% ACN over 7 min); UVDetector: 254/220 nm. The products was seperated with the followingconditions: Column: Phenomenex Lux 5u Cellulose-4£¬AXIA Packed, 2.12×25cm,5 um; Mobile Phases, A: Hexanes (containing 0.1% TFA) and B: EtOH(30% EtOH over 25 min); UV Detector: 254/220 nm; This afforded the titlecompounds as follows: 6.6 mg (6%) of3-[(7S)-6-(methoxycarbonyl)-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-2-yl]-2R-phenylpropanoicacid (assumed stereochemistry, first eluting isomer, RT=14.37 min) as alight yellow solid and 8.7 mg (7%) of3-[(7S)-6-(methoxycarbonyl)-7-methyl-3-(oxan-4-yl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-2-yl]-2S-phenylpropanoicacid (assumed stereochemistry, first eluting isomer, RT=18.48 min) as alight yellow solid.

First eluting isomer: ¹H-NMR: (CD₃OD, 400 MHz) δ (ppm): 7.82-7.74 (m,2H), 7.41-7.32 (m, 5H), 4.85-4.82 (m, 2H), 4.28-4.22 (m, 1H), 4.14-4.10(m, 1H), 4.03-3.98 (m, 2H), 3.79 (s, 3H), 3.74-3.64 (m, 2H), 3.49-3.48(m, 1H), 3.06-3.04 (m, 1H), 2.96-2.95 (m, 1H), 2.61-2.55 (m, 1H),2.45-2.35 (m, 1H), 2.21-2.15 (m, 1H), 1.98-1.90 (m, 2H), 1.16 (d, J=6.8Hz, 4H). MS: (ES, m/z): 478[M+H]⁺

Second eluting isomer: ¹H-NMR: (CD₃OD, 400 MHz) δ (ppm): 7.78-7.73 (m,2H), 7.39-7.31 (m, 5H), 4.87-4.80 (m, 2H), 4.28-4.24 (m, 1H), 4.12-4.09(m, 1H), 4.03-3.97 (m, 2H), 3.79 (s, 3H), 3.74-3.64 (m, 2H), 3.48-3.47(m, 1H), 3.03-2.98 (m, 2H), 2.55-2.35 (m, 2H), 2.21-2.19 (m, 1H),1.98-1.85 (m, 2H), 1.14-1.11 (m, 4H). MS: (ES, m/z): 478[M+H]⁺

The following examples in TABLE 8 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Examples 139 and 140.

TABLE 8 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 141 and 142

1^(st) eluting isomer = 518 2^(nd) eluting isomer = 518 1^(st) elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.36-7.13 (m, 7H), 4.74-4.72 (m,1H), 4.60 (s, 2H), 4.39 (s, 2H), 4.18-4.14 (m, 2H), 3.76 (s, 3H),3.68-3.62 (m, 1H), 3.38-3.31 (m, 1H), 3.13-3.10 (m, 1H), 2.93- 2.89 (m,1H), 2.33-1.97 (m, 5H), 1.76-1.69 (m, 3H), 1.57-1.45 (m, 1H), 1.13-1.06(m, 4H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.39-7.12(m, 7H), 4.74-4.71 (m, 1H), 4.60 (d, J = 3.3 Hz, 2H), 4.42-4.36 (m, 2H),4.26-4.18 (m, 2H), 3.76 (s, 3H), 3.70-3.62 (m, 1H), 3.36 (d, J = 7.8 Hz,1H), 3.18-3.11 (m, 1H), 2.91-2.85 (m, 1H), 2.28-2.12 (m, 3H), 2.31- 1.92(m, 5H), 1.74-1.53 (m, 1H), 1.10-1.01 (m, 4H) 143 and 144

1^(st) eluting isomer = 554 2^(nd) eluting isomer = 554 1^(st) elutingisomer ¹H-NMR (DMSO-d6, 300 MHz) δ (ppm): 7.44-7.19 (m, 7H), 4.66-4.61(m, 1H), 4.37 (s, 1H), 4.12-4.07 (m, 1H), 3.67-3.45 (m, 6H), 3.21- 3.14(m, 1H), 3.08-2.95 (m, 4H), 2.85-2.76 (m, 1H), 2.25-2.18 (m, 2H),2.16-2.09 (m, 2H), 2.08- 1.96 (m, 1H), 1.76-1.47 (m, 3H), 1.36-1.25 (m,1H), 1.17 (d, J = 6.6 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR (DMSO-d6, 300MHz) δ (ppm): 7.46-7.31 (m, 3H), 7.29-7.20 (m, 4H), 4.66-4.60 (m, 1H),4.51- 4.43 (m, 1H), 4.12-4.08 (m, 1H), 3.67-3.59 (m, 4H), 3.13-2.96 (m,6H), 2.75-2.82 (m, 1H), 2.30- 1.97 (m, 6H), 1.77-1.53 (m, 4H), 1.08-1.06(d, J = 6.6 Hz, 3H) 145 and 146

1^(st) eluting isomer = 507 2^(nd) eluting isomer = 507 1^(st) elutingisomer ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.58-7.52 (m, 1H), 7.35-7.30 (m,5H), 7.14-7.10 (m, 1H), 4.77- 4.74 (m, 1H), 4.61-4.58 (m, 1H), 4.29-4.23(m, 1H), 4.11-4.02 (m, 1H), 3.82 (s, 3H), 3.80-3.79 (m, 1H), 3.76-3.61(m, 4H), 3.39- 3.35 (m, 1H), 3.11-3.05 (m, 1H), 2.96-2.90 (m, 1H),2.63-2.49 (m, 6H), 2.15-2.09 (m, 1H), 1.71- 1.63 (m, 1H), 1.12-1.08 (m,3H) 2^(nd) eluting isomer ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.60-7.52 (m,1H), 7.40-7.31 (m, 5H), 7.16-7.11 (m, 1H), 4.77-4.75 (m, 1H), 4.64-4.61(m, 1H), 4.30-4.28 (m, 1H), 4.08- 4.04 (m, 1H), 3.82 (s, 3H), 3.80- 3.79(m, 1H), 3.76-3.62 (m, 4H), 3.39-3.35 (m, 1H), 3.14-3.06 (m, 1H),2.97-2.93 (m, 1H), 2.64- 2.50 (m, 6H), 2.21-2.11 (m, 1H), 1.68-1.65 (m,1H), 1.12-1.08 (m, 3H) 147 and 148

1^(st) eluting isomer = 504 2^(nd) eluting isomer = 504 1^(st) elutingisomer ¹H-NMR (CF₃CO₂D, 300 MHz) δ (ppm): 7.86 (d, J = 9.0 Hz, 1H),7.44- 7.26 (m, 4H), 7.26-7.13 (m, 3H), 6.78 (s, 1H), 4.98-4.77 (m, 1H),4.45-4.35 (m, 1H), 4.32-4.07 (m, 2H), 4.04-3.84 (m, 4H), 3.81- 3.56 (m,3H), 3.25-3.07 (m, 2H), 3.07-2.81 (m, 2H), 2.37-2.20 (m, 1H), 2.09-1.90(m, 2H), 1.89- 1.70 (m, 3H), 1.70-1.43 (m, 3H), 1.15 (d, J = 6.9 Hz, 3H)2^(nd) eluting isomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.48-7.33 (m,3H), 7.26-7.09 (m, 3H), 6.99 (d, J = 8.1 Hz, 1H), 4.72 (d, J = 8.1 Hz,1H), 4.41 (s, 1H), 4.12-3.80 (m, 2H), 3.73 (s, 3H), 3.66-3.50 (m, 1H),3.23- 2.75 (m, 5H), 2.50-2.00 (m, 3H), 1.82-1.18 (m, 7H), 1.11 (d, J =6.3 Hz, 4H) 149 and 150

1^(st) eluting isomer = 491 2^(nd) eluting isomer = 491 1^(st) elutingisomer ¹H-NMR (DMSO-d6, 300 MHz) δ (ppm): 7.41 (d, J = 7.1 Hz, 2H),7.32- 7.12 (m, 5H), 4.63-4.59 (m, 1H), 4.14-4.07 (m, 2H), 3.88-3.82 (m,1H), 3.67-3.55 (m, 4H), 3.09- 2.89 (m, 4H), 2.83-2.72 (m, 1H), 2.45-2.40(m, 1H), 2.17-2.09 (m, 1H), 2.04-1.70 (m, 1H), 1.62- 1.44 (m, 3H),1.32-1.20 (m, 3H), 1.05 (d, J = 6.6 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR(DMSO-d6, 300 MHz) δ (ppm): 7.41 (d, J = 7.1 Hz, 2H), 7.34- 7.13 (m,5H), 4.67-4.59 (m, 1H), 4.18-4.08 (m, 2H), 3.93-3.87 (m, 1H), 3.68-3.50(m, 4H), 3.11- 2.92 (m, 4H), 2.81-2.72 (m, 1H), 2.40-2.00 (m, 3H),1.61-1.41 (m, 3H), 1.40-1.10 (m, 3H), 1.05 (d, J = 6.6 Hz, 3H) 151 and152

1^(st) eluting isomer = 506 2^(nd) eluting isomer = 506 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.45-7.14 (m, 7H), 4.76-4.68 (m,1H), 4.27-4.02 (m, 2H), 3.76 (s, 3H), 3.70-3.61 (m, 1H), 3.41- 3.26 (m,5H), 3.19-3.14 (m, 1H), 2.91-2.79 (m, 1H), 2.37-1.99 (m, 5H), 1.89-1.81(m, 1H), 1.79- 1.58 (m, 1H), 1.51-1.15 (m, 2H), 1.10 (d, J = 6.6 Hz,3H), 1.01- 0.90 (m, 1H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ(ppm): 7.48-7.11 (m, 7H), 4.76-4.69 (m, 1H), 4.30-4.16 (m, 1H), 4.09-4.02 (m, 1H), 3.76 (s, 3H), 3.68- 3.62 (m, 1H), 3.38-3.29 (m, 5H), 3.16(m, 1H), 2.87 (m, 1H), 2.36-2.02 (m, 5H), 1.89-1.81 (m, 1H), 1.72-1.61(m, 1H), 1.43-1.18 (m, 2H), 1.12 (d, J = 6.7 Hz, 3H), 1.11-1.03 (m, 1H)153 and 154

1^(st) eluting isomer = 501 2^(nd) eluting isomer = 501 1^(st) elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.39-7.35 (m, 3H), 7.35-7.25 (m,3H), 7.25-7.21 (m, 1H), 4.88- 4.73 (m, 1H), 4.26-4.21 (m, 1H), 4.07-4.04(m, 1H), 3.78 (s, 3H), 3.70-3.65 (m, 1H), 3.51-3.39 (m, 2H), 3.33-3.14(m, 1H), 2.95-2.91 (m, 1H), 2.91-2.77 (m, 1H), 2.28- 2.22 (m, 3H),2.22-2.11 (m, 2H), 1.98-1.90 (m, 1H), 1.74-1.71 (m, 1H), 1.63-1.60 (m,1H), 1.12 (d, J = 6.7 Hz, 3H), 1.01 (s, 1H) 2^(nd) eluting isomer ¹H-NMR(CD₃OD, 400 MHz) δ (ppm): 7.43-7.22 (m, 7H), 4.91-4.73 (m, 1H),4.30-4.06 (m, 1H), 4.04- 4.02 (m, 1H), 3.78 (s, 3H), 3.72- 3.66 (m, 1H),3.38-3.33 (m, 1H), 3.18-3.16 (m, 1H), 2.97-2.81 (m, 2H), 2.31-2.15 (m,5H), 2.13- 1.87 (m, 2H), 1.87-1.62 (m, 2H), 1.15 (d, J = 6.6 Hz, 3H),1.16- 1.14 (m, 1H) 155 and 156

1^(st) eluting isomer = 478 2^(nd) eluting isomer = 478 1^(st) elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53-7.48 (m, 1H), 7.37-7.22 (m,6H), 4.76-4.71 (m, 1H), 4.48- 4.42 (m, 1H), 4.22-4.16 (m, 1H), 4.06-3.87(m, 2H), 3.79 (s, 3H), 3.70-3.66 (m, 1H), 3.55-3.49 (m, 1H), 3.38-3.34(m, 1H), 3.21- 3.12 (m, 2H), 2.93-2.87 (m, 1H), 2.52-2.45 (m, 1H),2.31-2.18 (m, 1H), 2.09-2.01 (m, 1H), 1.89- 1.80 (m, 2H), 1.73-1.65 (m,1H), 1.12 (d, J = 6.4 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 400MHz) δ (ppm): 7.49 (d, J = 9.0 Hz, 1H), 7.47- 7.34 (m, 3H), 7.33-7.31(m, 2H), 7.24-7.20 (m, 1H), 4.78-4.75 (m, 1H), 4.43-4.32 (m, 1H), 4.21-4.16 (m, 1H), 4.06 (t, J = 10.8 Hz, 1H), 4.03-3.88 (m, 2H), 3.78 (s,3H), 3.76-3.63 (m, 1H), 3.54- 3.49 (m, 1H), 3.44-3.35 (m, 1H), 3.19-3.12(m, 1H), 2.93-2.82 (m, 1H), 2.43-2.18 (m, 2H), 1.74- 1.61 (m, 3H),1.33-1.17 (m, 1H), 1.15 (d, J = 6.4 Hz, 3H) 157 and 158

1^(st) eluting isomer = 478 2^(nd) eluting isomer = 478 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.80-7.70 (m, 2H), 7.32-7.21 (m,5H), 4.60-4.73 (m, 1H), 4.21 (t, J = 15.0 Hz, 1H), 3.97-3.83 (m, 3H),3.70 (s, 3H), 3.64-3.48 (m, 2H), 3.35-3.25 (m, 1H), 3.02- 2.81 (m, 2H),2.58-2.38 (m, 1H), 2.20-2.05 (m, 2H), 1.98-1.75 (m, 3H), 1.21 (m, 1H),1.05 (d, J = 6.9 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ(ppm): 7.80-7.70 (m, 2H), 7.32-7.21 (m, 5H), 4.62-4.50 (m, 1H), 4.20 (t,J = 15.0 Hz, 1H), 3.93 (d, J = 9.0 Hz, 2H), 3.92-3.83 (m, 2H), 3.71 (s,3H), 3.69-3.48 (m, 2H), 2.98- 2.86 (m, 2H), 2.38-2.08 (m, 2H), 1.88-1.60(m, 3H), 1.32-1.20 (m, 2H), 1.04 (d, J = 3.3 Hz, 3H) 159, 160, 161 and162

1^(st) eluting isomer = 506 2^(nd) eluting isomer = 506 3^(rd) elutingisomer = 506 4^(th) eluting isomer = 506 1^(st) eluting isomer ¹H-NMR(CD₃OD, 400 MHz) δ (ppm): 7.45-7.26 (m, 7H), 4.76-4.74 (m, 1H),4.30-4.22 (m, 2H), 3.76 (s, 3H), 3.71-3.66 (m, 1H), 3.43- 3.30 (m, 3H),3.15-3.12 (m, 1H), 2.92-2.87 (m, 1H), 2.22-2.17 (m, 2H), 1.98-1.72 (m,5H), 1.57- 1.54 (m, 2H), 1.13-1.09 (m, 5H) 2^(nd) eluting isomer ¹H-NMR(CD₃OD, 400 MHz) δ (ppm): 7.43-7.25 (m, 7H), 4.76-4.73 (m, 1H),4.25-4.22 (m, 2H), 3.76 (s, 3H), 3.66-3.64 (m, 1H), 3.43- 3.29 (m, 3H),3.13-3.11 (m, 1H), 2.94-2.90 (m, 1H), 2.22-2.17 (m, 2H), 1.98-1.72 (m,5H), 1.57- 1.54 (m, 2H), 1.12-0.96 (m, 5H) 3^(rd) eluting isomer ¹H-NMR(CD₃OD, 400 MHz) δ (ppm): 7.45-7.24 (m, 7H), 4.76-4.74 (m, 1H),4.30-4.22 (m, 2H), 3.76 (s, 3H), 3.71-3.66 (m, 1H), 3.43- 3.30 (m, 3H),3.15-3.12 (m, 1H), 2.92-2.87 (m, 1H), 2.22-2.21 (m, 1H), 2.04-1.72 (m,7H), 1.41- 1.38 (m, 1H), 1.12-1.07 (m, 5H) 4^(th) eluting isomer ¹H-NMR(CD₃OD, 400 MHz) δ (ppm): 7.46-7.25 (m, 7H), 4.76-4.74 (m, 1H),4.30-4.22 (m, 2H), 3.76 (s, 3H), 3.71-3.66 (m, 1H), 3.43- 3.30 (m, 3H),3.15-3.12 (m, 1H), 2.92-2.87 (m, 1H), 2.22-2.21 (m, 1H), 2.04-1.72 (m,7H), 1.41- 1.38 (m, 1H), 1.20-1.09 (m, 5H) 163, 164, 165 and 166

1^(st) eluting isomer = 506 2^(nd) eluting isomer = 506 3^(rd) elutingisomer = 506 4^(th) eluting isomer = 506 1^(st) eluting isomer ¹H-NMR(CD₃OD, 400 MHz) δ (ppm): 7.45-7.26 (m, 7H), 4.76-4.74 (m, 1H),4.30-4.22 (m, 2H), 3.76 (s, 3H), 3.71-3.66 (m, 1H), 3.43- 3.30 (m, 3H),3.15-3.12 (m, 1H), 2.92-2.87 (m, 1H), 2.22-2.17 (m, 2H), 1.98-1.72 (m,5H), 1.57- 1.54 (m, 2H), 1.13-1.09 (m, 5H) 2^(nd) eluting isomer ¹H-NMR(CD₃OD, 400 MHz) δ (ppm): 7.43-7.25 (m, 7H), 4.76-4.73 (m, 1H),4.25-4.22 (m, 2H), 3.76 (s, 3H), 3.66-3.64 (m, 1H), 3.43- 3.29 (m, 3H),3.13-3.11 (m, 1H), 2.94-2.90 (m, 1H), 2.22-2.17 (m, 2H), 1.98-1.72 (m,5H), 1.57- 1.54 (m, 2H), 1.12-0.96 (m, 5H) 3^(rd) eluting isomer ¹H-NMR(CD₃OD, 400 MHz) δ (ppm): 7.45-7.24 (m, 7H), 4.76-4.74 (m, 1H),4.30-4.22 (m, 2H), 3.76 (s, 3H), 3.71-3.66 (m, 1H), 3.43- 3.30 (m, 3H),3.15-3.12 (m, 1H), 2.92-2.87 (m, 1H), 2.22-2.21 (m, 1H), 2.04-1.72 (m,7H), 1.41- 1.38 (m, 1H), 1.12-1.07 (m, 5H) 4^(th) eluting isomer ¹H-NMR(CD₃OD, 400 MHz) δ (ppm): 7.46-7.25 (m, 7H), 4.76-4.74 (m, 1H),4.30-4.22 (m, 2H), 3.76 (s, 3H), 3.71-3.66 (m, 1H), 3.43-3.30 (m, 3H),3.15-3.12 (m, 1H), 2.92- 2.87 (m, 1H), 2.22-2.21 (m, 1H), 2.04-1.72 (m,7H), 1.41-1.38 (m, 1H), 1.20-1.09 (m, 5H) 167 and 168

1^(st) eluting isomer = 524 2^(nd) eluting isomer = 524 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.43-7.36 (m, 2H), 7.32-7.02 (m,1H), 7.15-7.02 (m, 2H), 7.00- 6.99 (m, 1H), 4.76-4.73 (m, 1H), 4.34-4.23(m, 2H), 3.70-3.67 (m, 4H), 3.40-3.32 (m, 4H), 3.13- 3.07 (m, 1H),2.93-2.87 (m, 1H), 2.32-2.13 (m, 5H), 1.96 (d, J = 12.6 Hz, 1H),1.76-1.69 (m, 1H), 1.56-1.19 (m, 3H), 1.12 (d, J = 6.6 Hz, 3H) 2^(nd)eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.41-7.34 (m, 2H),7.34-7.24 (m, 1H), 7.24-7.16 (m, 1H), 7.16- 7.14 (m, 1H), 7.00-6.96 (m,1H), 4.77-4.72 (m, 1H), 4.34 (s, 1H), 4.14 (s, 1H), 3.77 (s, 3H), 3.77-3.65 (m, 1H), 3.41-3.31 (s, 5H), 3.16-3.13 (m, 1H), 2.91-2.85 (m, 1H),2.40-2.13 (m, 5H), 1.98- 1.94 (m, 1H), 1.76-1.69 (m, 1H), 1.50-1.46 (m,1H), 1.34-1.26 (m, 2H), 1.13 (d, J = 6.7 Hz, 3H) 169 and 170

1^(st) eluting isomer = 524 2^(nd) eluting isomer = 524 1^(st) elutingisomer ¹H-NMR (DMSO-d6, 400 MHz) δ (ppm): 7.40-7.07 (m, 6H), 4.64-4.59(m, 1H), 4.28-4.14 (m, 2H), 3.65 (s, 3H), 3.58-3.52 (m, 1H), 3.34 (s,4H), 3.16-3.11 (m, 1H), 3.04- 2.96 (m, 1H), 2.81-2.67 (m, 1H), 2.14-2.01(m, 5H), 1.86-1.83 (m, 1H), 1.62-1.57 (m, 1H), 1.36- 1.23 (m, 3H),1.04-1.03 (m, 3H) 2^(nd) eluting isomer ¹H-NMR (DMSO-d6, 400 MHz) δ(ppm): 7.46-7.10 (m, 6H), 4.64-4.59 (m, 1H), 4.36-4.17 (m, 2H), 3.65 (s,3H), 3.65-3.57 (m, 1H), 3.34 (s, 4H), 3.16-3.11 (m, 1H), 3.04- 2.96 (m,1H), 2.81-2.67 (m, 1H), 2.14-2.01 (m, 5H), 1.86-1.83 (m, 1H), 1.62-1.23(m, 4H), 1.05- 1.04 (m, 3H) 171 and 172

1^(st) eluting isomer = 539 2^(nd) eluting isomer = 539 1^(st) elutingisomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.47-7.42 (m, 1H), 7.39-7.32 (m,1H), 7.22 (s, 3H), 4.74-4.72 (m, 1H), 4.35-4.10 (m, 2H), 3.76 (s, 3H),3.70-3.60 (m, 1H), 3.35- 3.31 (m, 5H), 3.30-2.93 (m, 2H), 2.26-2.18 (m,5H), 2.16-1.90 (m, 1H), 1.80-1.12 (m, 4H), 1.10 (d, J = 6.6 Hz, 3H)2^(nd) eluting isomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.48-7.22 (m,6H), 4.74-4.72 (m, 1H), 4.40-4.11 (m, 2H), 3.76- 3.65 (m, 4H), 3.40-3.32(m, 5H), 3.31-2.80 (m, 2H), 2.28-2.15 (m, 5H), 1.89-1.30 (m, 5H), 1.28(d, J = 67.2 Hz, 3H) 173 and 174

1^(st) eluting isomer = 539 2^(nd) eluting isomer = 539 1^(st) elutingisomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.41-7.25 (m, 6H), 4.74-4.72 (m,1H), 4.30-4.05 (m, 2H), 3.76 (s, 3H), 3.70-3.60 (m, 1H), 3.40- 3.30 (m,5H), 3.20-2.92 (m, 2H), 2.25-2.16 (m, 5H), 1.90-1.29 (m, 5H), 1.10 (d, J= 6.6 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm):7.36-7.23 (m, 6H), 4.80-4.70 (m, 1H), 4.40-4.95 (m, 2H), 3.75 (s, 3H),3.70-3.60 (m, 1H), 3.40- 3.30 (m, 5H), 3.29-2.80 (m, 2H), 2.40-2.05 (m,5H), 1.98-1.45 (m, 2H), 1.50-1.11 (m, 6H) 175 and 176

1^(st) eluting isomer = 542 2^(nd) eluting isomer = 542 1^(st) elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47 (d, J = 9.0 Hz, 1H), 7.42-7.37 (m, 2H), 7.24-7.14 (m, 2H), 4.79-4.71 (m, 1H), 4.44-4.28 (m, 1H),4.28-4.22 (m, 1H), 3.76- 3.70 (m, 4H), 3.49-3.35 (m, 4H), 3.17-3.09 (m,1H), 3.09-3.00 (m, 1H), 2.94-2.87 (m, 1H), 2.38- 2.18 (m, 5H), 2.01-1.92(m, 1H), 1.77-1.69 (m, 1H), 1.55-1.38 (m, 3H), 1.11 (d, J = 6.7 Hz, 3H)2^(nd) eluting isomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47 (d, J = 9.0Hz, 1H), 7.42- 7.37 (m, 2H), 7.24-7.14 (m, 2H), 4.79-4.71 (m, 1H),4.44-4.28 (m, 1H), 4.28-4.22 (m, 1H), 3.76- 3.70 (m, 4H), 3.49-3.35 (m,5H), 3.17-3.09 (m, 1H), 2.94-2.87 (m, 1H), 2.38-2.18 (m, 5H), 2.01- 1.96(m, 1H), 1.77-1.69 (m, 1H), 1.55-1.38 (m, 3H), 1.11 (d, J = 6.7 Hz, 3H)177 and 178

1^(st) eluting isomer = 520 2^(nd) eluting isomer = 520 1^(st) elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.83-7.75 (m, 2H), 7.27-7.12 (m,4H), 4.81-4.80 (m, 1H), 4.58- 4.50 (m, 1H), 4.20-4.17 (m, 1H), 3.99-3.94(m, 1H), 3.80 (s, 3H), 3.74-3.68 (m, 1H), 3.49-3.33 (m, 4H), 3.17-2.91(m, 2H), 2.44- 2.02 (m, 9H), 1.97-1.82 (m, 1H), 1.54-1.44 (m, 1H),1.38-1.22 (m, 2H), 1.16 (d, J = 6.7 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR(CD₃OD, 300 MHz) δ (ppm): 7.83-7.75 (m, 2H), 7.27-7.12 (m, 4H),4.81-4.80 (m, 1H), 4.58- 4.50 (m, 1H), 4.20-4.17 (m, 1H), 3.99-3.94 (m,1H), 3.80 (s, 3H), 3.74-3.68 (m, 1H), 3.49-3.33 (m, 4H), 3.17-2.91 (m,2H), 2.44- 2.02 (m, 9H), 1.97-1.82 (m, 1H), 1.54-1.44 (m, 1H), 1.38-1.22(m, 2H), 1.16 (d, J = 6.7 Hz, 3H) 179 and 180

1^(st) eluting isomer = 520 2^(nd) eluting isomer = 520 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.36-7.27 (m, 2H), 7.26-7.18 (m,2H), 7.07-7.02 (m, 2H), 4.82- 4.68 (m, 1H), 4.11-4.03 (m, 1H), 4.02-3.92(m, 1H), 3.77 (s, 3H), 3.68-3.52 (m, 1H), 3.43-3.34 (m, 4H), 3.21-3.04(m, 1H), 2.99- 2.80 (m, 1H), 2.33-1.99 (m, 8H), 1.97-1.82 (m, 1H),1.79-1.62 (m, 1H), 1.49-1.04 (m, 6H), 0.98- 0.81 (m, 1H) 2^(nd) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.41-7.27 (m, 2H), 7.26-7.17 (m,2H), 7.11-7.01 (m, 2H), 4.79- 4.62 (m, 1H), 4.23-4.06 (m, 1H), 4.02-3.89(m, 1H), 3.75 (s, 3H), 3.75-3.56 (m, 1H), 3.41-3.33 (m, 4H), 3.24-3.09(m, 1H), 2.93- 2.77 (m, 1H), 2.36-1.99 (m, 8H), 1.95-1.82 (m, 1H),1.79-1.61 (m, 1H), 1.52-1.07 (m, 6H), 1.06- 0.93 (m, 1H) 181 and 182

1^(st) eluting isomer = 554 2^(nd) eluting isomer = 554 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.50-7.29 (m, 2H), 7.22 (d, 1H),7.06-6.89 (m, 2H), 4.81-4.68 (m, 1H), 4.27-4.21 (m, 1H), 4.00 (t, J =7.5 Hz, 1H), 3.81 (S, 3H), 3.78 (S, 3H), 3.70-3.56 (m, 1H), 3.48-3.34(m, 5H), 3.23-3.06 (m, 1H), 2.99-2.83 (m, 1H), 2.34- 2.09 (m, 5H),1.93-1.85 (m, 1H), 1.79-1.62 (m, 1H), 1.52-1.22 (m, 2H), 1.20-1.07 (m,4H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.47-7.32 (m,2H), 7.25 (d, J = 12.2 Hz, 1H), 7.10-6.91 (m, 2H), 4.81-4.68 (m, 1H),4.32-4.26 (m, 1H), 4.05-3.96 (m, 1H), 3.80 (S, 3H), 3.78 (S, 3H),3.72-3.58 (m, 1H), 3.48-3.34 (m, 5H), 3.25- 3.08 (m, 1H), 2.95-2.79 (m,1H), 2.38-2.10 (m, 5H), 1.93-1.85 (m, 1H), 1.78-1.65 (m, 1H), 1.54- 1.20(m, 3H), 1.14 (d, J = 6.6 Hz, 3H) 183 and 184

1^(st) eluting isomer = 538 2^(nd) eluting isomer = 538 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.45-7.28 (m, 2H), 7.14-7.08 (m,2H), 7.00-6.97 (m, 1H), 4.73- 4.71 (m, 1H), 4.24-4.10 (m, 1H), 4.07-4.04(m, 1H), 3.77 (s, 3H), 3.64-3.61 (m, 1H), 3.40-3.32 (m, 5H), 3.23-3.07(m, 1H), 2.96- 2.88 (m, 1H), 2.34-2.07 (m, 8H), 1.93 (d, J = 12.5 Hz,1H), 1.79- 1.62 (m, 1H), 1.53-1.17 (m, 3H), 1.11 (d, J = 6.7 Hz, 3H)2^(nd) eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.37-7.31 (m,2H), 7.16-7.01 (m, 2H), 7.00-6.96 (m, 1H), 4.90 (s, 1H), 4.26-4.10 (m,1H), 4.01- 3.95 (m, 1H), 3.76 (s, 3H), 3.70- 3.61 (m, 1H), 3.42-3.35 (m,5H), 3.16-3.04 (m, 1H), 2.93-2.80 (m, 1H), 2.38-2.07 (m, 8H), 1.95- 1.85(m, 1H), 1.73-1.67 (m, 1H), 1.48-1.35 (m, 1H), 1.32-1.18 (m, 2H), 1.13(d, J = 6.7 Hz, 3H) 185 and 186

1^(st) eluting isomer = 553 2^(nd) eluting isomer = 553 1^(st) elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.83-7.75 (m, 2H), 7.27-7.12 (m,4H), 4.81-4.80 (m, 1H), 4.58- 4.50 (m, 1H), 4.20-4.17 (m, 1H), 3.99-3.94(m, 1H), 3.80 (s, 3H), 3.74-3.68 (m, 1H), 3.49-3.33 (m, 4H), 3.17-2.91(m, 2H), 2.44- 2.02 (m, 9H), 1.97-1.82 (m, 1H), 1.54-1.44 (m, 1H),1.38-1.22 (m, 2H), 1.16 (d, J = 6.7 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR(CD₃OD, 300 MHz) δ (ppm): 7.83-7.75 (m, 2H), 7.27-7.12 (m, 4H),4.81-4.80 (m, 1H), 4.58- 4.50 (m, 1H), 4.20-4.17 (m, 1H), 3.99-3.94 (m,1H), 3.80 (s, 3H), 3.74-3.68 (m, 1H), 3.49-3.33 (m, 4H), 3.17-2.91 (m,2H), 2.44- 2.02 (m, 9H), 1.97-1.82 (m, 1H), 1.54-1.44 (m, 1H), 1.38-1.22(m, 2H), 1.16 (d, J = 6.7 Hz, 3H) 187 and 188

1^(st) eluting isomer = 461 2^(nd) eluting isomer = 461 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.36-7.27 (m, 2H), 7.26-7.18 (m,2H), 7.07-7.02 (m, 2H), 4.82- 4.68 (m, 1H), 4.11-4.03 (m, 1H), 4.02-3.92(m, 1H), 3.77 (s, 3H), 3.68-3.52 (m, 1H), 3.43-3.34 (m, 4H), 3.21-3.04(m, 1H), 2.99- 2.80 (m, 1H), 2.33-1.90 (m, 8H), 1.97-1.82 (m, 1H),1.79-1.62 (m, 1H), 1.49-1.04 (m, 6H), 0.98- 0.81 (m, 1H) 2^(nd) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.41-7.27 (m, 2H), 7.26-7.17 (m,2H), 7.11-7.01 (m, 2H), 4.79- 4.62 (m, 1H), 4.23-4.06 (m, 1H), 4.02-3.89(m, 1H), 3.75 (s, 3H), 3.75-3.56 (m, 1H), 3.41-3.33 (m, 4H), 3.24-3.09(m, 1H), 2.93- 2.77 (m, 1H), 2.36-1.99 (m, 8H), 1.95-1.82 (m, 1H),1.79-1.61 (m, 1H), 1.52-1.07 (m, 6H), 1.06- 0.93 (m, 1H) 189 and 190

1^(st) eluting isomer = 489 2^(nd) eluting isomer = 489 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.50-7.29 (m, 2H), 7.22 (d, 1H),7.06-6.89 (m, 2H), 4.81-4.68 (m, 1H), 4.27-4.21 (m, 1H), 4.00 (t, J =7.5 Hz, 1H), 3.81 (S, 3H), 3.78 (S, 3H), 3.70-3.56 (m, 1H), 3.48-3.34(m, 5H), 3.23-3.06 (m, 1H), 2.99-2.83 (m, 1H), 2.34- 2.09 (m, 5H),1.93-1.85 (m, 1H), 1.79-1.62 (m, 1H), 1.52-1.22 (m, 2H), 1.20-1.07 (m,4H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.47-7.32 (m,2H), 7.25 (d, J = 12.2 Hz, 1H), 7.10-6.91 (m, 2H), 4.81-4.68 (m, 1H),4.32-4.26 (m, 1H), 4.05-3.96 (m, 1H), 3.80 (S, 3H), 3.78 (S, 3H),3.72-3.58 (m, 1H), 3.48-3.34 (m, 5H), 3.25- 3.08 (m, 1H), 2.95-2.79 (m,1H), 2.38-2.10 (m, 5H), 1.93-1.85 (m, 1H), 1.78-1.65 (m, 1H), 1.54- 1.20(m, 3H), 1.14 (d, J = 6.6 Hz, 3H) 191 and 192

1^(st) eluting isomer = 540 2^(nd) eluting isomer = 540 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.58-7.49 (m, 3H), 7.39-6.90 (m,7H), 6.78 (d, J = 9 Hz, 1H), 4.81- 4.67 (m, 1H), 4.29-4.01 (m, 1H), 3.75(s, 3H), 3.63-3.44 (m, 1H), 3.27-3.10 (m, 2H), 3.02-2.89 (m, 1H),2.36-2.15 (m, 1H), 1.81- 1.61 (m, 1H), 1.49-1.04 (m, 1H), 1.17-1.04 (d,J = 6.6 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm):7.66-7.49 (m, 3H), 7.32 (d, J = 9 Hz, 1H), 7.26-6.99 (m, 7H), 6.80 (d, J= 9 Hz, 1H), 4.83-4.67 (m, 1H), 4.12-3.98 (m, 1H), 3.74 (s, 3H),3.63-3.49 (m, 1H), 3.27- 3.11 (m, 2H), 3.01-2.79 (m, 1H), 2.34-2.16 (m,1H), 1.83-1.61 (m, 1H), 1.19 (d, J = 6.6 Hz, 3H) 193 and 194

1^(st) eluting isomer = 447 2^(nd) eluting isomer = 447 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.83-7.75 (m, 2H), 7.27-7.12 (m,4H), 4.81-4.80 (m, 1H), 4.58- 4.50 (m, 1H), 4.20-4.17 (m, 1H), 3.99-3.94(m, 1H), 3.80 (s, 3H), 3.74-3.68 (m, 1H), 3.49-3.33 (m, 4H), 3.17-2.91(m, 2H), 2.44- 2.02 (m, 9H), 1.97-1.82 (m, 1H), 1.54-1.44 (m, 1H),1.38-1.22 (m, 2H), 1.16 (d, J = 6.7 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR(CD₃OD, 300 MHz) δ (ppm): 7.83-7.75 (m, 2H), 7.27-7.12 (m, 4H),4.81-4.80 (m, 1H), 4.58- 4.50 (m, 1H), 4.20-4.17 (m, 1H), 3.99-3.94 (m,1H), 3.80 (s, 3H), 3.74-3.68 (m, 1H), 3.49-3.33 (m, 4H), 3.17-2.91 (m,2H), 2.44- 2.02 (m, 9H), 1.97-1.82 (m, 1H), 1.54-1.44 (m, 1H), 1.38-1.22(m, 2H), 1.16 (d, J = 6.7 Hz, 3H) 195 and 196

1^(st) eluting isomer = 463 2^(nd) eluting isomer = 463 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.36-7.27 (m, 2H), 7.26-7.18 (m,2H), 7.07-7.02 (m, 2H), 4.82- 4.68 (m, 1H), 4.11-4.03 (m, 1H), 4.02-3.92(m, 1H), 3.77 (s, 3H), 3.68-3.52 (m, 1H), 3.43-3.34 (m, 4H), 3.21-3.04(m, 1H), 2.99- 2.80 (m, 1H), 2.33-1.99 (m, 8H), 1.97-1.82 (m, 1H),1.79-1.62 (m, 1H), 1.49-1.04 (m, 6H), 0.98- 0.81 (m, 1H) 2^(nd) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.41-7.27 (m, 2H), 7.26-7.17 (m,2H), 7.11-7.01 (m, 2H), 4.79- 4.62 (m, 1H), 4.23-4.06 (m, 1H), 4.02-3.89(m, 1H), 3.75 (s, 3H), 3.75-3.56 (m, 1H), 3.41-3.33 (m, 4H), 3.24-3.09(m, 1H), 2.93- 2.77 (m, 1H), 2.36-1.99 (m, 8H), 1.95-1.82 (m, 1H),1.79-1.61 (m, 1H), 1.52-1.07 (m, 6H), 1.06- 0.93 (m, 1H) 197 and 198

1^(st) eluting isomer = 449 2^(nd) eluting isomer = 449 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.50-7.29 (m, 2H), 7.22 (d, 1H),7.06-6.89 (m, 2H), 4.81-4.68 (m, 1H), 4.27-4.21 (m, 1H), 4.00 (t, J =7.5 Hz, 1H), 3.81 (S, 3H), 3.78 (S, 3H), 3.70-3.56 (m, 1H), 3.48-3.34(m, 5H), 3.23-3.06 (m, 1H), 2.99-2.83 (m, 1H), 2.34- 2.09 (m, 5H),1.93-1.85 (m, 1H), 1.79-1.62 (m, 1H), 1.52-1.22 (m, 2H), 1.20-1.07 (m,4H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.47-7.32 (m,2H), 7.25 (d, J = 12.2 Hz, 1H), 7.10-6.91 (m, 2H), 4.81-4.68 (m, 1H),4.32-4.26 (m, 1H), 4.05-3.96 (m, 1H), 3.80 (S, 3H), 3.78 (S, 3H),3.72-3.58 (m, 1H), 3.48-3.34 (m, 5H), 3.25- 3.08 (m, 1H), 2.95-2.79 (m,1H), 2.38-2.10 (m, 5H), 1.93-1.85 (m, 1H), 1.78-1.65 (m, 1H), 1.54- 1.20(m, 3H), 1.14 (d, J = 6.6 Hz, 3H) 199 and 200

1^(st) eluting isomer = 492 2^(nd) eluting isomer = 492 1^(st) elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.82-7.74 (m, 2H), 7.39-7.33 (m,5H), 4.55-4.52 (m, 1H), 4.24- 4.21 (m, 1H), 4.01-3.95 (m, 1H), 3.79-3.69(m, 5H), 3.04-3.00 (m, 1H), 2.96-2.93 (m, 1H), 2.42- 2.38 (m, 1H),2.25-2.21 (m, 2H), 2.19-2.10 (m, 1H), 2.04-1.98 (m, 2H), 1.92-1.87 (m,1H), 1.60- 1.56 (m, 1H), 1.43-1.39 (m, 1H), 1.28-1.22 (m, 2H), 1.16 (d,J = 6.4 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm):7.39-7.23 (m, 7H), 4.75-4.71 (m, 1H), 4.91-4.17 (m, 2H), 3.75 (s, 3H),3.70-3.64 (m, 2H), 3.39- 3.36 (m, 1H), 3.13-3.11 (m, 1H), 2.93-2.89 (m,1H), 2.28-2.14 (m, 3H), 2.08-2.05 (m, 1H), 1.95- 1.87 (m, 2H), 1.73-1.69(m, 1H), 1.58-1.53 (m, 1H), 1.33-1.29 (m, 1H), 1.11 (d, J = 6.8 Hz, 3H),1.00-0.95 (m, 1H) 201 and 202

1^(st) eluting isomer = 492 2^(nd) eluting isomer = 492 1^(st) elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.86-7.80 (m, 2H), 7.45-7.32 (m,5H), 5.17-5.11 (m, 1H), 4.34- 4.31 (m, 2H), 4.01-3.95 (m, 1H), 3.80 (s,3H), 3.60-3.55 (m, 1H), 3.04-2.90 (m, 2H), 2.54-2.41 (m, 2H), 2.24-2.18(m, 1H), 2.09- 1.97 (m, 3H), 1.91-1.71 (m, 4H), 1.30-1.28 (m, 1H), 1.15(d, J = 6.4 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ(ppm): 7.79-7.73 (m, 2H), 7.38-7.31 (m, 5H), 4.81-4.76 (m, 1H), 4.29-4.20 (m, 2H), 3.93-3.90 (m, 1H), 3.81-3.75 (m, 4H), 2.99-2.96 (m, 2H),2.43-2.42 (m, 1H), 2.23- 2.04 (m, 3H), 1.90-1.78 (m, 3H), 1.68-1.61 (m,2H), 1.30-1.28 (m, 1H), 1.13-1.06 (m, 4H) 203 and 204

1^(st) eluting isomer = 492 2^(nd) eluting isomer = 492 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.42-7.30 (m, 4H), 7.28-7.24 (m,3H), 4.76-4.71 (m, 1H), 4.32- 4.30 (m, 1H), 4.16-4.15 (m, 1H), 3.75 (s,3H), 3.71-3.65 (m, 1H), 3.57-3.56 (m, 1H), 3.35-3.33 (m, 1H), 3.16-3.12(m, 1H), 2.90- 2.86 (m, 1H), 2.24-2.19 (m, 1H), 2.11-1.99 (m, 3H),1.97-1.85 (m, 2H), 1.74-1.69 (m, 1H), 1.52- 1.49 (m, 2H), 1.33-1.30 (m,1H), 1.13 (d, J = 6.4 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 300MHz) δ (ppm): 7.43-7.24 (m, 7H), 4.76-4.72 (m, 1H), 4.28-4.25 (m, 2H),3.76- 3.67 (m, 5H), 3.39-3.33 (m, 1H), 3.14-3.12 (m, 1H), 2.94-2.90 (m,1H), 2.23-1.95 (m, 5H), 1.78- 1.71 (m, 2H), 1.35-1.28 (m, 2H), 1.12 (d,J = 6.4 Hz, 3H), 1.03- 1.00 (m, 1H) 205 and 206

1^(st) eluting isomer = 492 2^(nd) eluting isomer = 492 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.41-7.24 (m, 7H), 4.75-4.71 (m,1H), 4.25-4.16 (m, 2H), 3.75 (s, 3H), 3.69-3.65 (m, 1H), 3.54- 3.52 (m,1H), 3.35-3.33 (m, 1H), 3.13-3.09 (m, 1H), 2.93-2.89 (m, 1H), 2.23-2.22(m, 1H), 2.06- 1.97 (m, 3H), 1.91-1.85 (m, 2H), 1.73-1.68 (m, 1H),1.51-1.29 (m, 3H), 1.11 (d, J = 6.4 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR(CD₃OD, 300 MHz) δ (ppm): 7.41-7.24 (m, 7H), 4.75-4.71 (m, 1H),4.25-4.16 (m, 2H), 3.75 (s, 3H), 3.69-3.65 (m, 1H), 3.54- 3.52 (m, 1H),3.35-3.33 (m, 1H), 3.13-3.09 (m, 1H), 2.93-2.89 (m, 1H), 2.23-2.22 (m,1H), 2.06- 1.97 (m, 3H), 1.91-1.85 (m, 2H), 1.73-1.68 (m, 1H), 1.51-1.29(m, 3H), 1.11 (d, J = 6.4 Hz, 3H 207 and 208

1^(st) eluting isomer = 476 2^(nd) eluting isomer = 476 1^(st) elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.85-7.75 (m, 2H), 7.37-7.32 (m,5H), 4.86-4.82 (m, 1H), 4.50- 4.40 (m, 1H), 4.24-4.20 (m, 1H), 3.99-3.93(m, 1H), 3.80 (s, 3H), 3.74-3.70 (m, 1H), 2.99-2.97 (m, 2H), 2.26-2.20(m, 2H), 2.14- 2.12 (m, 1H), 2.02-1.83 (m, 4H), 1.78-1.76 (m, 1H),1.52-1.42 (m, 1H), 1.45-1.30 (m, 2H), 1.20- 1.12 (m, 4H) 2^(nd) elutingisomer ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): .83-7.79 (m, 2H), 7.38-7.32 (m,5H), 4.86-4.82 (m, 1H), 4.50- 4.40 (m, 1H), 4.24-4.20 (m, 1H), 3.99-3.93(m, 1H), 3.80 (s, 3H), 3.74-3.70 (m, 1H), 3.04-2.93 (m, 2H), 2.26-2.20(m, 2H), 2.14- 2.12 (m, 1H), 2.02-1.83 (m, 4H), 1.78-1.76 (m, 1H),1.52-1.42 (m, 1H), 1.45-1.30 (m, 2H), 1.17- 1.14 (m, 4H) 209, 210, 211and 212

1^(st) eluting isomer = 501 2^(nd) eluting isomer = 501 3^(rd) elutingisomer = 501 4^(th) eluting isomer = 501 1^(st) eluting isomer ¹H-NMR(CD₃OD, 400 MHz) δ (ppm): 7.88-7.71 (m, 2H), 7.49-7.27 (m, 5H),4.63-4.42 (m, 1H), 4.36- 4.18 (m, 1H), 4.02-3.91 (m, 1H), 3.83 (s, 3H),3.80-3.62 (m, 1H), 3.11-2.96 (m, 2H), 2.82-2.69 (m, 1H), 2.40-2.21 (m,3H), 2.21- 2.09 (m, 1H), 2.09-1.98 (m, 2H), 1.98-1.86 (m, 1H), 1.86-1.61(m, 2H), 1.38-1.27 (m, 1H), 1.22-1.11 (m, 4H) 2^(nd) eluting isomer¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.91-7.73 (m, 2H), 7.49-7.27 (m, 5H),4.71-4.42 (m, 1H), 4.29- 4.12 (m, 1H), 4.11-3.92 (m, 1H), 3.82-3.66 (m,4H), 3.12-2.93 (m, 2H), 2.83-2.59 (m, 1H), 2.37- 1.50 (m, 9H), 1.32-1.25(m, 2H), 1.18 (d, J = 6.6 Hz, 3H) 3^(rd) eluting isomer ¹H-NMR (CD₃OD,400 MHz) δ (ppm): 7.51-7.40 (m, 1H), 7.40-7.31 (m, 3H), 7.28-7.19 (m,2H), 7.19-7.06 (m, 1H), 4.81-4.68 (m, 1H), 4.41-4.23 (m, 1H), 4.11-3.99(m, 1H), 3.77 (s, 3H), 3.70-3.59 (m, 1H), 3.29-3.20 (m, 1H), 3.20- 3.06(m, 1H), 3.02-2.84 (m, 2H), 2.42-2.31 (m, 1H), 2.31-2.15 (m, 2H),2.15-2.02 (m, 2H), 1.93-1.82 (m, 1H), 1.74-1.62 (m, 2H), 1.51- 1.39 (m,1H), 1.19-1.04 (m, 4H) 4^(th) eluting isomer ¹H-NMR (CD₃OD, 400 MHz) δ(ppm): 7.50-7.18 (m, 7H), 4.79-4.61 (m, 1H), 4.49-4.31 (m, 1H), 4.19-4.03 (m, 1H), 3.78 (s, 3H), 3.72- 3.57 (m, 1H), 3.27-3.09 (m, 2H),3.02-2.80 (m, 2H), 2.55-2.33 (m, 1H), 2.33-2.04 (m, 4H), 1.96- 1.79 (m,1H), 1.79-1.53 (m, 2H), 1.53-1.31 (m, 1H), 1.25-1.01 (m, 4H) 213, 214,215 and 216

1^(st) eluting isomer = 501 2^(nd) eluting isomer = 501 3^(rd) elutingisomer = 501 4^(th) eluting isomer = 501 1^(st) eluting isomer ¹H-NMR(CD₃OD, 300 MHz) δ (ppm): 7.82-7.66 (m, 2H), 7.49-7.21 (m, 5H),4.83-4.78 (m, 1H), 4.38- 4.24 (m, 1H), 4.93-3.78 (m, 4H), 3.73-3.58 (m,1H), 3.46-3.35 (m, 2H), 3.16-2.81 (m, 2H), 2.61- 1.77 (m, 9H), 1.71-1.53(m, 1H), 1.16 (d, J = 6.6 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD,300 MHz) δ (ppm): 7.81-7.67 (m, 2H), 7.50-7.29 (m, 5H), 4.88-4.79 (m,1H), 4.71-4.46 (m, 1H), 4.34-4.19 (m, 1H), 3.99-3.87 (m, 1H), 3.79 (s,3H), 3.63-3.47 (m, 1H), 3.47- 3.37 (m, 1H), 3.11-2.94 (m, 2H), 2.62-2.42(m, 1H), 2.42-2.14 (m, 3H), 2.02-1.61 (m, 5H), 1.26- 1.04 (m, 4H) 3^(rd)eluting isomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.51-7.21 (m, 7H),4.81-4.61 (m, 1H), 4.39-4.22 (m, 1H), 4.13-4.01 (m, 1H), 3.76 (s, 3H),3.71-3.55 (m, 1H), 3.44-3.33 (m, 1H), 3.24-3.07 (m, 1H), 3.02-2.81 (m,2H), 2.52-2.13 (m, 3H), 2.09-1.91 (m, 2H), 1.83-1.71 (m, 3H), 1.62-1.43(m, 1H), 1.14-1.11 (m, 4H) 4^(th) eluting isomer ¹H-NMR (CD₃OD, 300 MHz)δ (ppm): 7.43-7.25 (m, 7H), 4.79-4.68 (m, 1H), 4.46-4.32 (m, 1H),4.26-4.07 (m, 1H), 3.82-3.61 (m, 4H), 3.43-3.32 (m, 1H), 3.23- 3.06 (m,1H), 2.96-2.83 (m, 2H), 2.54-2.38 (m, 1H), 2.33-2.04 (m, 4H), 1.99-1.83(m, 1H), 1.83- 1.54 (m, 2H), 1.44-1.31 (m, 1H), 1.24-0.98 (m, 4H)

Example 217: methyl(S)-2-benzyl-3-(2-(1,1-dioxidothiomorpholino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(2S)-5-amino-6-[(2,2-dimethoxyethyl)amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 50-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(500 mg, 1.67 mmol, Intermediate 1) was dissolved in toluene (10 mL).Then 2,2-dimethoxyethan-1-amine (1.09 g, 10.37 mmol), sodiumtert-butoxide (480 mg, 4.99 mmol), 3rd Generation BrettPhos precatalyst(150 mg, 0.17 mmol) and BrettPhos (180 mg, 0.34 mmo) were addedsuccessively. The resulting solution was stirred for 2 h at 110° C.under nitrogen atmosphere. The reaction mixture was cooled and theresulting solids were filtered out. The filtrate was concentrated undervacuum. The residue was subjected to purification by FCC eluting withethyl acetate/petroleum ether (3:1). This afforded the title compound(530 mg, 98%) as a brown oil. MS: (ES, m/z): 324 [M+H]⁺.

Step 2. Synthesis of methyl(7S)-2-benzyl-3-(2,2-dimethoxyethyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 100-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-[(2,2-dimethoxyethyl)amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(530 mg, 1.64 mmol) was dissolved in toluene (15 mL). Then2-phenylacetaldehyde (423 mg, 3.52 mmol) was added. The resultingsolution was stirred for 14 h at room temperature. The resulting mixturewas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (1:1). This affordedthe title compound (520 mg, 75%) as a yellow oil. MS: (ES, m/z): 424[M+H]⁺.

Step 3. Synthesis of methyl(7S)-2-benzyl-7-methyl-3-(2-oxoethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 100-mL round-bottom flask, methyl(7S)-2-benzyl-3-(2,2-dimethoxyethyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(520 mg, 1.23 mmol) was dissolved in tetrahydrofuran (4 mL). Thenhydrochloric acid (4 M, 8 mL) was added. The resulting solution wasstirred for 3 h at 60° C. The reaction mixture was cooled to roomtemperature. The resulting solution was diluted with 40 mL of water andextracted with 2×90 mL of ethyl acetate and the organic layers werecombined, dried over anhydrous sodium sulfate, filtered and concentratedunder vacuum. This afforded the title compound (450 mg, crude) as ayellow solid. MS: (ES, m/z): 396 [M+H₂O]*.

Step 4. Synthesis of methyl(S)-2-benzyl-3-(2-(1,1-dioxidothiomorpholino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask, methyl(7S)-2-benzyl-7-methyl-3-(2-oxoethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(80 mg, 0.21 mmol) was dissolved in methanol (6 mL). Then thiomorpholine1,1-dioxide (143 mg, 1.06 mmol) and acetic acid (127 mg, 2.11 mmol) wereadded. The mixture was stirred at room temperature for 30 min. To themixture was added sodium cyanoborohydride (134 mg, 2.13 mmol) at 0° C.The resulting solution was stirred for 12 h at room temperature. Thenwater (20 mL) was added slowly. The resulting solution was extractedwith 2×60 mL of ethyl acetate. The organic layers were combined, driedover anhydrous sodium sulfate, filtered and concentrated under vacuum.The crude product was purified by Prep-HPLC with the followingconditions: Column, XBridge C18 OBD Prep Column, 100 Å, 5 μm, 19 mm×250mm; mobile phase, A: water (containing 10 mmol/L NH₄HCO₃) and B: ACN(25.0% to 40.0% ACN over 10 min); UV Detector: 254 nm. This afforded thetitle compound (31 mg, 29%) as a white solid. ¹H-NMR (DMSO-d₆, 400 MHz)δ (ppm): 7.36-7.20 (m, 7H), 4.69-4.59 (m, 1H), 4.33 (s, 2H), 4.24-4.13(m, 2H), 3.66 (s, 3H), 3.12-2.94 (m, 5H), 2.90-2.76 (m, 5H), 2.61-2.51(m, 2H), 2.20-2.06 (m, 1H), 1.66-1.56 (m, 1H), 1.05 (d, J=6.8 Hz, 3H).MS: (ES, m/z): 497 [M+H]⁺.

The following examples in TABLE 9 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Examples 217.

TABLE 9 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 218

461 ¹H-NMR (DMSO-d6, 400 MHz) δ (ppm): 7.35-7.19 (m, 7H), 4.69-4.59 (m,1H), 4.52 (s, 4H), 4.28 (s, 2H), 4.04-3.94 (m, 2H), 3.66 (s, 3H), 3.16(s, 4H), 3.10-2.99 (m, 1H), 2.80 (dt, J = 16.8, 6.0 Hz, 1H), 2.48-2.42(m, 2H), 2.18-2.08 (m, 1H), 1.65-1.56 (m, 1H), 1.05 (d, J = 6.4 Hz, 3H)methyl (S)-3-(2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)ethyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 219

461 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.43 (d, J = 8.8 Hz, 1H), 7.36-7.16(m, 5H), 7.07 (d, J = 8.8 Hz, 1H), 4.88-4.71 (m, 1H), 4.47 (t, J = 7.5Hz, 2H), 4.42-4.32 (m, 2H), 3.90 (t, J = 7.2 Hz, 2H), 3.78 (s, 3H), 3.50(s, 2H), 3.36-3.19 (m, 1H), 3.11-2.94 (m, 3H), 2.80 (t, J = 7.5 Hz, 2H),2.64- 2.42 (m, 2H), 2.37-2.19 (m, 1H), 1.82-1.65 (m, 1H), 1.17 (d, J =6.6 Hz, 3H) methyl (S)-3-(2-(1-oxa-6-azaspiro[3.3]heptan-6-yl)ethyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 220

509 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.90-7.85 (m, 1H), 7.68-7.65 (m,1H), 7.45-7.30 (m, 5H), 4.88 (s, 3H), 4.69 (s, 2H), 4.47-4.43 (m, 2H),4.00-3.98 (m, 4H), 3.80 (s, 3H), 3.12-2.93 (m, 4H), 2.27-2.20 (m, 3H),1.89-1.86 (m, 1H), 1.16 (d, J = 6.4 Hz, 3H) methyl(S)-2-benzyl-3-(2-(1,1-dioxido-1-thia-6-azaspiro[3.3]heptan-6-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline- 6-carboxylate 221

475 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.44 (d, J = 8.8 Hz, 1H), 7.32-7.27(m, 2H), 7.26- 7.21 (m, 3H), 7.09 (d, J = 8.8 Hz, 1H), 4.81-4.79 (m,1H), 4.59 (t, J = 5.2 Hz, 4H), 4.55-4.29 (m, 2H), 4.03 (t, J = 7.5 Hz,2H), 3.78 (s, 3H), 3.28-3.23 (m, 1H), 3.12-2.95 (m, 1H), 2.68 (s, 2H),2.57-2.19 (m, 5H), 2.07 (t, J = 7.0 Hz, 2H), 1.77-1.71 (m, 1H), 1.17 (d,J = 6.6 Hz, 3H) methyl (S)-3-(2-(2-oxa-6-azaspiro[3.4]octan-6-yl)ethyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 222

489 ¹H-NMR (DMSO-d6, 400 MHz) δ (ppm): 7.48 (d, J = 8.6 Hz, 1H),7.35-7.28 (m, 2H), 7.28- 7.20 (m, 4H), 4.69-4.59 (m, 1H), 4.38-4.28 (m,4H), 4.20-4.07 (m, 2H), 3.66 (s, 3H), 3.12-2.99 (m, 1H), 2.84-2.75 (m,1H), 2.46-2.35 (m 2H), 2.34- 2.22 (m, 4H), 2.21-2.07 (m, 3H), 1.77-1.55(m, 5H), 1.05 (d, J = 6.8 Hz, 3H) methyl(S)-3-(2-(1-oxa-7-azaspiro[3.5]nonan-7-yl)ethyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 223

489 ¹H-NMR (DMSO-d6, 400 MHz) δ (ppm): 7.35-7.19 (m, 7H), 4.69-4.59 (m,1H), 4.31 (s, 2H), 4.23 (s, 3H), 4.19-4.10 (m, 3H), 3.66 (s, 3H), 3.10-3.00 (m, 1H), 2.80-2.75 (m, 1H), 2.35-2.09 (m, 7H), 1.75-1.55 (m, 5H),1.05 (d, J = 6.4 Hz, 3H) methyl (S)-3-(2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)ethyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 224

448 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.43 (d, J = 8.7 Hz, 1H), 7.32-7.26(m, 2H), 7.26- 7.19 (m, 3H), 7.09 (d, J = 8.8 Hz, 1H), 4.83-4.77 (m,1H), 4.45-4.33 (m, 2H), 4.03 (t, J = 7.2 Hz, 2H), 3.78 (s, 3H),3.31-3.23 (m, 1H), 3.07-2.98 (m, 1H), 2.88 (t, J = 4.9 Hz, 4H),2.42-2.22 (m, 8H), 1.77-1.70 (m, 1H), 1.17 (d, J = 6.6 Hz, 3H) methyl(S)-2-benzyl-7-methyl-3-(2-(piperazin-1-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5- f]quinoline-6-carboxylate225

462 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.43 (d, J = 8.8 Hz, 1H), 7.39-7.27(m, 2H), 7.24-7.13 (m, 3H), 7.09 (d, J = 8.8 Hz, 1H), 4.83-4.79 (m, 1H),4.51-4.29 (m, 2H), 4.02 (t, J = 7.2 Hz, 2H), 3.78 (s, 3H), 3.31-3.23 (m,1H), 3.08-3.00 (m, 1H), 2.46-2.22 (m, 14H), 1.79-1.68 (m, 1H), 1.17 (d,J = 6.7 Hz, 3H) methyl (S)-2-benzyl-7-methyl-3-(2-(4-methylpiperazin-1-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 226

453 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.55 (d, J = 9 Hz, 1H), 7.24 (s,1H), 7.26-7.21 (m, 1H), 7.06 (d, J = 8.7 Hz, 1H), 6.19-6.00 (m, 1H),4.82-4.77 (m, 1H), 4.76-4.65 (m, 2H), 4.01-3.88 (m, 2H), 3.88-3.73 (m,3H), 3.73-3.61 (m, 4H), 3.50-3.41 (m, 2H), 3.32-3.13 (m, 1H), 3.11-2.89(m, 1H), 2.57- 2.49 (m, 2H), 2.49-2.39 (m, 4H), 2.35-2.19 (m, 1H),1.79-1.64 (m, 1H), 1.16 (d, J = 6.6 Hz, 3H) methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-morpholinoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 227

466 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.52 (d, J = 1.8 Hz, 1H), 7.43 (d,J = 8.9 Hz, 1H), 7.25-7.18 (m, 1H), 7.06 (d, J = 8.8 Hz, 1H), 6.13 (t, J= 2.1 Hz, 1H), 4.85-4.66 (m, 3H), 3.89 (t, J = 6.7 Hz, 2H), 3.78 (s,3H), 3.51-3.36 (m, 2H), 3.32- 3.15 (m, 1H), 3.08-2.91 (m, 1H), 2.66-2.13(m, 14H), 1.81-1.64 (m, 1H), 1.16 (d, J = 6.6 Hz, 3H) methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(4-methylpiperazin-1-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline- 6-carboxylate 228

465 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.55 (s, 1H), 7.45 (d, J = 8.8 Hz,1H), 7.29 (s, 1H), 7.06 (d, J = 8.8 Hz, 1H), 6.16 (s, 1H), 4.89-4.58 (m,7H), 3.88-3.69 (m, 5H), 3.50-3.38 (m, 2H), 3.31- 3.14 (m, 5H), 3.07-2.96(m, 1H), 2.69-2.51 (m, 2H), 2.39-2.26 (m, 1H), 1.82-1.69 (m, 1H), 1.18(d, J = 6.8 Hz, 3H) methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5- f]quinoline-6-caiboxylate 229

479 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.42-7.40 (m, 2H), 7.35-7.29 (m,1H), 7.09 (d, J = 8.7 Hz, 1H), 6.56 (d, J = 9.0 Hz, 1H), 6.08- 6.05 (m,1H), 4.80-4.78 (m, 1H), 4.46-4.38 (m, 2H), 4.22-4.18 (m, 2H), 3.78 (s,3H), 3.44-3.37 (m, 2H), 3.21-3.16 (m, 1H), 3.01-2.96 (m, 1H), 2.90-2.86(m, 4H), 2.64-2.60 (m, 2H), 2.50-2.48 (m, 4H), 2.27-2.25 (m, 1H),1.76-1.68 (m, 1H), 1.15 (d, J = 6.6 Hz, 3H) methyl(S)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3-(2-(piperazin-1-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 230

493 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.43-7.40 (m, 2H), 7.34-7.28 (m,1H), 7.09 (d, J = 8.7 Hz, 1H), 6.58 (d, J = 9.0 Hz, 1H), 6.09- 6.04 (m,1H), 4.80-4.78 (m, 1H), 4.48-4.39 (m, 2H), 4.18-4.15 (m, 2H), 3.73 (s,3H), 3.43-3.37 (m, 2H), 3.22-3.18 (m, 1H), 3.01-2.96 (m, 1H), 2.64-2.52(m, 6H), 2.42-2.23 (m, 8H), 1.76-1.71 (m, 1H), 1.15 (d, J = 6.9 Hz, 3H)methyl (S)-7-methyl-3-(2-(4-methylpiperazin-1-yl)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline- 6-carboxylate 231

492 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.42-7.40 (m, 2H), 7.35-7.29 (m,1H), 7.08 (d, J = 9.0 Hz, 1H), 6.57 (d, J = 8.7 Hz, 1H), 6.08- 6.05 (m,1H), 4.80-4.78 (m, 1H), 4.66 (s, 4H), 4.46-4.38 (m, 2H), 4.07-4.02 (m,2H), 3.78 (s, 3H), 3.41-3.34 (m, 2H), 3.29-3.18 (m, 5H), 3.01- 2.96 (m,1H), 2.69-2.65 (m, 2H), 2.30-2.20 (m, 1H), 1.77-1.71 (m, 1H), 1.15 (d, J= 6.6 Hz, 3H) methyl (S)-3-(2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5- f]quinoline-6-carboxylate232

439 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.73-7.61 (m, 1H), 7.60-7.48 (m,2H), 7.41- 7.29 (m, 1H), 6.32-6.30 (m, 1H), 5.78 (s, 2H), 4.94-4.78 (m,1H), 4.69-4.36 (m, 2H), 3.93- 3.67 (m, 7H), 3.39-3.14 (m, 1H), 3.09-2.96(m, 1H), 2.80-2.45 (m, 6H), 2.36-2.17 (m, 1H), 1.82-1.66 (m, 1H), 1.16(d, J = 6.8 Hz, 3H) methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-morpholinoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 233

466 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.71 (d, J = 6.8 Hz, 1H), 7.51 (d,J = 8.8 Hz, 1H), 7.34-7.28 (m, 1H), 7.19 (d, J = 8.4 Hz, 1H), 6.57 (d, J= 8.8 Hz, 1H), 6.18 (td, J = 6.8, 1.2 Hz, 1H), 5.55 (d, J = 14.8 Hz,1H), 5.49 (d, J = 14.8 Hz, 1H), 4.83-4.74 (m, 1H), 4.58-4.36 (m, 2H),3.77 (s, 3H), 3.71 (s, 4H), 3.27-3.16 (m, 1H), 3.01 (d, J = 17.2, 5.6Hz, 1H), 2.70-2.40 (m, 6H), 2.30-2.19 (m, 1H), 1.77-1.68 (m, 1H), 1.14(d, J = 6.8 Hz, 3H) methyl (S)-7-methyl-3-(2-morpholinoethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate

Examples 234 and 235: methyl(7S)-2-benzyl-7-methyl-3-[2-[(4S)-1-oxa-6-azaspiro[3.4]octan-6-yl]ethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(7S)-2-benzyl-7-methyl-3-[2-[(4R)-1-oxa-6-azaspiro[3.4]octan-6-yl]ethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(7S)-2-benzyl-7-methyl-3-[2-[(4S)-1-oxa-6-azaspiro[3.4]octan-6-yl]ethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(7S)-2-benzyl-7-methyl-3-[2-[(4R)-1-oxa-6-azaspiro[3.4]octan-6-yl]ethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(7S)-2-benzyl-7-methyl-3-(2-oxoethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(100 mg, 0.26 mmol) was dissolved in methanol (5 mL). Then1-oxa-6-azaspiro[3.4]octane (89.9 mg, 0.79 mmol) and acetic acid (79.6mg, 1.33 mmol) were added. The mixture was stirred for 30 min at roomtemperature. To the mixture was added sodium cyanoborohydride (167.1 mg,2.66 mmol) at 0° C. The resulting solution was stirred for 14 h at roomtemperature. The resulting solution was diluted with 10 mL of water andextracted with 3×10 mL of ethyl acetate. The organic layers werecombined, dried over anhydrous sodium sulfate, filtered and concentratedunder vacuum. The crude product was purified by Prep-HPLC with thefollowing conditions: Column, XBridge Prep C18 OBD Column, 19×150 mm 5μm; mobile phase, A: Water (containing 10 mmol/L NH₄HCO₃) and B: ACN(30.0% to 55.0% ACN over 7 min); UV Detector: 254 nm. The product waspurified by Chiral-Prep-HPLC with the following conditions: Column,CHIRAL ART Cellulose-SB, 2×25 cm,5 μm; mobile phase, Hexane and ethanol(hold 30.0% ethanol in 34 min); UV Detector: 220/254 nm. This affordedthe title compounds as follows: 9.7 mg (8%) of methyl(7S)-2-benzyl-7-methyl-3-[2-[(4S)-1-oxa-6-azaspiro[3.4]octan-6-yl]ethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, first eluting isomer, RT=21.50 min) as a whitesolid and 12.7 mg (10%) of methyl(7S)-2-benzyl-7-methyl-3-[2-[(4R)-1-oxa-6-azaspiro[3.4]octan-6-yl]ethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, second eluting isomer, RT=22.71 min) as awhite solid

First eluting isomer: ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.44 (d, J=8.7Hz, 1H), 7.33-7.28 (m, 2H), 7.27-7.23 (m, 3H), 7.12 (d, J=8.8 Hz, 1H),4.83-4.77 (m, 1H), 4.49-4.40 (m, 4H), 4.05 (s, 2H), 3.78 (s, 3H),3.28-3.23 (m, 1H), 3.06-2.92 (m, 1H), 2.90 (d, J=10.6 Hz, 1H), 2.69-1.91(m, 10H), 1.77-1.70 (m, 1H), 1.17 (d, J=6.7 Hz, 3H). MS: (ES, m/z): 475[M+H]⁺.

Second eluting isomer: ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.50 (s, 1H),7.35 (d, J=5.0 Hz, 4H), 7.34-7.26 (m, 2H), 4.83-4.78 (m, 1H), 4.51-4.42(m, 6H), 3.79 (s, 4H), 3.38-3.20 (m, 1H), 3.12-3.00 (m, 1H), 2.75-2.62(m, 6H), 2.50-1.66 (m, 5H), 1.17 (d, J=6.7 Hz, 3H). MS: (ES, m/z): 475[M+H]⁺.

Examples 236, 237 and 238: methyl(S)-2-benzyl-3-(2-((2S,6R)-2,6-dimethylmorpholino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate,methyl(S)-2-benzyl-3-(2-((2R,6R)-2,6-dimethylmorpholino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate,and methyl(S)-2-benzyl-3-(2-((2S,6S)-2,6-dimethylmorpholino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(7S)-2-benzyl-3-[2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]ethyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(7S)-2-benzyl-3-[2-[(2R,6R)-2,6-dimethylmorpholin-4-yl]ethyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(7S)-2-benzyl-3-[2-[(2S,6S)-2,6-dimethylmorpholin-4-yl]ethyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(7S)-2-benzyl-7-methyl-3-(2-oxoethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(70 mg, 0.19 mmol) was dissolved in methanol (5 mL). Then2,6-dimethylmorpholine (128 mg, 1.11 mmol) and acetic acid (67 mg, 1.12mmol) were added. The mixture was stirred at room temperature for 30 minagain. To the mixture was added sodium cyanoborohydride (70 mg, 1.11mmol). The resulting solution was stirred for 12 h at room temperature.Water (10 ml) was added and the resulting solution was extracted with2×60 mL of ethyl acetate. The organic layers were combined, dried oversodium sulfate, filtered and concentrated under vacuum. The crudeproduct was purified by Prep-HPLC with the following conditions: Column,XBridge C18 OBD Prep Column, 100 Å, 5 μm, 19 mm×250 mm; mobile phase A:water (containing 10 mmol/L NH₄HCO₃) and B: ACN (30.0% to 45.0% ACN over10 min); UV Detector: 254 nm. The crude product was purified by Prep-SFCwith the following conditions: Column, CHIRALCEL OJ-H, 2×25 cm, 5 μm;mobile phase, CO₂ (90%), EtOH (2 mM NH₃/MeOH) (10%) and echo (0%); UVDetector: 220 nm. This afforded the title compounds as follows: 6.0 mg(7%) of methyl(7S)-2-benzyl-3-[2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]ethyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, first eluting isomer) as a white solid and 3.4mg (4%) of methyl(7S)-2-benzyl-3-[2-[(2R,6R)-2,6-dimethylmorpholin-4-yl]ethyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, second eluting isomer, RT=2.25 min) as a whitesolid and 3.9 mg (4%) of methyl(7S)-2-benzyl-3-[2-[(2S,6S)-2,6-dimethylmorpholin-4-yl]ethyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, third eluting isomer, RT=2.60 min) as a whitesolid.

First eluting isomer: ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.45 (d, J=8.0Hz, 1H), 7.32-7.27 (m, 2H), 7.26-7.16 (m, 3H), 7.10 (d, J=8.8 Hz, 1H),4.80 (h, J=6.0 Hz, 1H), 4.47-4.33 (m, 2H), 4.03 (s, 2H), 3.78 (s, 3H),3.63 (s, 2H), 3.34-3.23 (m, 1H), 3.04-2.98 (m, 1H), 2.54 (t, J=11.6 Hz,2H), 2.43-2.34 (m, 1H), 2.34-2.21 (m, 2H), 1.80-1.62 (m, 3H), 1.17 (d,J=6.8 Hz, 3H), 1.15-1.11 (m, 6H). MS: (ES, m/z): 477 [M+H]⁺.

Second eluting isomer: ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.55-7.41 (m,1H), 7.33-7.27 (m, 2H), 7.26-7.18 (m, 3H), 7.11 (d, J=8.4 Hz, 1H),4.85-4.75 (m, 1H), 4.43 (s, 2H), 4.10-3.90 (m, 4H), 3.78 (s, 3H),3.34-3.23 (m, 1H), 3.13-2.99 (m, 1H), 2.40-2.20 (m, 5H), 2.06-1.96 (m,2H), 1.80-1.70 (m, 1H), 1.23-1.13 (m, 9H). MS: (ES, m/z): 477 [M+H]⁺.

Third eluting isomer: ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.55-7.41 (m,1H), 7.33-7.27 (m, 2H), 7.26-7.17 (m, 3H), 7.11 (d, J=6.8 Hz, 1H),4.87-4.74 (m, 1H), 4.43 (s, 2H), 4.11-3.91 (m, 4H), 3.78 (s, 3H),3.35-3.23 (m, 1H), 3.13-2.98 (m, 1H), 2.46-2.17 (m, 5H), 2.04-1.94 (m,2H), 1.82-1.69 (m, 1H), 1.22-1.12 (m, 9H). MS: (ES, m/z): 477 [M+H]⁺.

Example 239: methyl(7S)-2-benzyl-3-[2-(2,2-dioxo-2lambda6-thia-6-azaspiro[3.3]heptan-6-yl)ethyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(7S)-2-benzyl-7-methyl-3-(2-[2-thia-6-azaspiro[3.3]heptan-6-yl]ethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(7S)-2-benzyl-7-methyl-3-(2-oxoethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(50 mg, 0.13 mmol) was dissolved in methanol (5 mL). Then2-thia-6-azaspiro[3.3]heptane oxalic acid salt (68 mg, 0.33 mmol) andsodium cyanoborohydride (13 mg, 0.21 mmol) were added. The resultingsolution was stirred overnight at room temperature. The resultingmixture was concentrated under vacuum. The residue was subjected topurification by FCC eluting with dichloromethane/methanol (10:1). Thisafforded the title compound (40 mg, 63%) as a white solid. MS: (ES,m/z): 477 [M+H]⁺.

Step 2. Synthesis of methyl(7S)-2-benzyl-3-[2-(2,2-dioxo-2lambda6-thia-6-azaspiro[3.3]heptan-6-yl)ethyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 8-mL round-bottom flask, methyl(7S)-2-benzyl-7-methyl-3-(2-[2-thia-6-azaspiro[3.3]heptan-6-yl]ethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(38 mg, 0.08 mmol) was dissolved in dichloromethane (4 mL). Then3-chloroperoxybenzoic acid (55 mg, 0.32 mmol) was added. The resultingsolution was stirred overnight at room temperature. The resultingmixture was concentrated under vacuum. The crude product was purified byPrep-HPLC with the following conditions: Column, XBridge C18 OBD PrepColumn, 100 Å, 5 μm, 19 mm×250 mm; mobile phase, A: water (10 mmol/LNH₄HCO₃) and B: ACN (20.0% to 40.0% ACN over 8 min); UV Detector: 254nm. This afforded the title compound (4.3 mg, 11%) as an off-whitesolid.

H-NMR: (CDCl₃, 400 MHz, ppm): 7.55 (d, J=8.6 Hz, 1H), 7.40-7.21 (m, 6H),4.81-4.58 (m, 1H), 4.75-4.45 (m, 4H), 4.18-3.68 (m, 8H), 3.57-3.19 (m,5H), 3.15-3.02 (m, 2H), 2.29-2.25 (m, 1H), 1.94-1.79 (m, 1H), 1.20 (d,J=6.8 Hz, 3H). MS: (ES, m/z): 509 [M+H]⁺.

Example 240: methyl(S)-3-(2-(4-acetylpiperazin-1-yl)ethyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(7S)-2-benzyl-7-methyl-3-[2-(piperazin-1-yl)ethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(30 mg, 0.07 mmol) was dissolved in dichloromethane (2 mL). Thenpyridine (16 mg, 0.20 mmol) was added, followed by of acetyl chloride(10.5 mg, 0.13 mmol). The resulting solution was stirred for 1 h at roomtemperature. The resulting mixture was concentrated under vacuum. Thecrude product was purified by Prep-HPLC with the following conditions:Column, XBridge C18 OBD Prep Column, 100 Å, 5 um, 19 mm×250 mm; mobilephase A: Water (containing 10 mmol/L NH₄HCO₃) and B: ACN (25.0% to 45.0%ACN over 8 min); UV Detector: 254 nm. This afforded the title compound(8.8 mg, 26%) as a white solid. ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.48(d, J=8.6 Hz, 1H), 7.33-7.28 (m, 2H), 7.24-7.20 (m, 3H), 7.09 (d, J=8.8Hz, 1H), 4.83-4.77 (m, 1H), 4.43-4.41 (m, 2H), 4.05 (t, J=7.0 Hz, 2H),3.79 (s, 3H), 3.58 (t, J=5.4 Hz, 2H), 3.40 (t, J=5.1 Hz, 2H), 3.39-3.23(m, 1H), 3.21-3.03 (m, 1H), 2.44-2.22 (m, 7H), 2.07 (s, 3H), 1.78-1.72(m, 1H), 1.17 (d, J=6.7 Hz, 3H). MS: (ES, m/z): 490 [M+H]⁺.

Example 241: methyl(S)-2-benzyl-7-methyl-3-(2-(4-(methylsulfonyl)piperazin-1-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(7S)-2-benzyl-7-methyl-3-[2-(piperazin-1-yl)ethyl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(30 mg, 0.07 mmol) was added in dichloromethane (2 mL). Thentriethylamine (20 mg, 0.20 mmol) was added, followed by methylsulfonylchloride (15.3 mg, 0.1 mmol). The resulting solution was stirred for 1 hat room temperature. The resulting mixture was concentrated undervacuum. The crude product was purified by Prep-HPLC with the followingconditions: Column, XBridge C18 OBD Prep Column, 100 Å, 5 um, 19 mm×250mm; mobile phase, A: Water (containing 10 mmol/L NH₄HCO₃) and B: ACN(25.0% to 45.0% ACN over 8 min); UV Detector: 254 nm. This afforded thetitle compound (17.3 mg, 48%) as a white solid. ¹H-NMR (CDCl₃, 300 MHz)δ (ppm): 7.50-7.47 (m, 1H), 7.33-7.28 (m, 3H), 7.25-7.20 (m, 2H), 7.08(d, J=8.8 Hz, 1H), 4.83-4.77 (m, 1H), 4.41 (s, 2H), 4.04 (t, J=7.1 Hz,2H), 3.79 (s, 3H), 3.32-3.23 (m, 1H), 3.23-3.16 (m, 4H), 3.16-3.03 (m,1H), 2.77 (s, 3H), 2.47-2.36 (m, 6H), 2.36-2.22 (m, 1H), 1.79-1.72 (m,1H), 1.17 (d, J=6.7 Hz, 3H). MS: (ES, m/z): 526 [M+H]⁺.

Example 242:methyl-(7S)-3-[2-(dimethylamino)ethyl]-7-methyl-2-(2-phenylethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask,methyl-(7S)-7-methyl-2-(2-phenylethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(30 mg, 0.09 mmol) was dissolved in tetrahydrofuran (3 mL). Then sodiumhydride (60%, 10 mg, 0.25 mmol) was added. The mixture was stirred for10 minutes at room temperature. Then (2-bromoethyl)dimethylamine (26 mg,0.17 mmol) was added. The resulting solution was stirred for 3 h at roomtemperature. The resulting mixture was diluted with 10 mL of water andextracted with 3×10 mL of ethyl acetate. The organic layers werecombined, dried over sodium sulfate, filtered and concentrated undervacuum. The residue was purified with the following conditions: Column:XBridge Prep C18 OBD Column 19*150 mm, 5 μm; Mobile Phase, A: water(containing 10 mmol/L NH₄HCO₃) and B: ACN (31% to 61% ACN over 8 min).UV Detector: 254 nm. This afforded the title compound (4.1 mg, 11%) as abrown oil. ¹H-NMR: (CDCl₃, 300 MHz) δ (ppm): 7.46 (d, J=9.0 Hz, 1H),7.33-7.13 (m, 5H), 7.10 (d, J=8.7 Hz, 1H), 4.84-4.78 (m, 1H), 4.06-4.02(m, 2H), 3.78 (s, 3H), 3.29-3.18 (m, 5H), 3.08-2.99 (m, 1H), 2.56-2.42(m, 2H), 2.25-2.23 (m, 7H), 1.78-1.73 (m, 1H), 1.15-1.10 (m, 3H). MS:(ES, m/z): 421[M+H]⁺

The following examples in TABLE 10 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Examples 242.

TABLE 10 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 243

456 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.52-7.48 (m, 1H), 7.33-7.23 (m,5H), 7.12 (d, J = 8.8 Hz, 1H), 4.83-4.78 (m, 1H), 4.42-4.38 (m, 2H),4.19- 4.17 (m, 2H), 3.78 (s, 3H), 3.33-3.25 (m, 1H), 3.09- 3.05 (m, 1H),2.72-2.67 (m, 5H), 2.29-2.23 (m, 1H), 2.06-1.96 (m, 2H), 1.78-1.77 (m,1H), 1.18-1.15 (m, 3H) methyl (S)-2-benzyl-7-methyl-3-(3-(methylsulfonyl)propyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 244

470 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.47 (d, J = 8.8 Hz, 1H), 7.29-7.27(m, 2H), 7.23- 7.19 (m, 3H), 7.11 (d, J = 8.8 Hz, 1H), 4.81-4.77 (m,1H), 4.13-4.09 (m, 2H), 3.79 (s, 3H), 3.29-3.15 (m, 5H), 3.16-3.00 (m,1H), 2.92-2.87 (m, 5H), 2.29- 2.19 (m, 3H), 1.75-1.70 (m, 1H), 1.17-1.13(m, 3H) methyl (S)-7-methyl-3-(3-(methylsulfonyl)propyl)-2-phenethyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 245

463 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.50 (d, J = 8.7 Hz, 1H), 7.34-7.20(m, 5H), 7.11 (d, J = 8.7 Hz, 1H), 4.84-4.78 (m, 1H), 4.03-3.99 (m, 2H),3.81 (s, 3H), 3.70-3.67 (m, 4H), 3.33-3.21 (m, 5H), 3.08-3.03 (m, 1H),2.58-2.50 (m, 2H), 2.46-2.43 (m, 4H), 2.29-2.25 (m, 1H), 1.79-1.73 (m,1H), 1.18 (d, J = 6.6 Hz, 3H). methyl(S)-7-methyl-3-(2-morpholinoethyl)-2-phenethyl-3,7,8,9-tetrahydro-6H-imidazo[4,5- f]quinoline-6-carboxylate246

407 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.46 (d, J = 8.7 Hz, 1H), 7.34-7.24(m, 5H), 7.14 (d, J = 8.7 Hz, 1H), 4.85-4.79 (m, 1H), 4.47-4.33 (m, 2H),4.13-4.08 (m, 2H), 3.80 (s, 3H), 3.35-3.24 (m, 1H), 3.15-3.01 (m, 2H),2.43-2.20 (m, 8H), 1.75-1.68 (m, 1H), 1.19 (d, J = 6.8 Hz, 3H) methyl(S)-2-benzyl-3-(2- (dimethylamino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate

Example 247: methyl(S)-2-cyclopropyl-7-methyl-3-(2-morpholinoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(2S)-5-amino-2-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 8-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(100 mg, 0.33 mmol, Intermediate 1) and 2-(morpholin-4-yl)ethan-1-amine(435 mg, 3.34 mmol,) were dissolved in toluene (5 mL) and then BrettPhos(60 mg, 0.11 mmol), sodium tert-butoxide (50 mg, 0.52 mmol) and 3^(rd)Generation BrettPhos precatalyst (60 mg, 0.07 mmol) were added. Theresulting solution was stirred for 3 h at 100° C. under nitrogenatmosphere. The reaction mixture was cooled and the resulting solidswere filtered out. The resulting mixture was concentrated under vacuum.The residue was subjected to purification by FCC eluting withdichloromethane/methanol (10:1). This afforded the title compound (130mg (crude)) as a yellow solid. MS: (ES, m/z): 349[M+H]⁺.

Step 2. Synthesis of methyl(S)-2-cyclopropyl-7-methyl-3-(2-morpholinoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 8-mL round-bottom flask, methyl(2S)-5-amino-2-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-1,2,3,4-tetrahydroquinoline-1-carboxylate(40 mg, 0.11 mmol) was dissolved in toluene (2 mL). Thencyclopropanecarbaldehyde (12 mg, 0.17 mmol) was added. The resultingsolution was stirred for 2 days at room temperature. The resultingmixture was concentrated under vacuum. The crude product was purified byPrep-HPLC with the following conditions: Column, XBridge C18 OBD PrepColumn, 100 Å, 5 μm, 19 mm×250 mm; mobile phase: A: water (containing0.05% NH₄OH) and B: ACN (25.0% ACN up to 50.0% in 8 min); UV Detector:254 nm. This afforded the title compound (10.8 mg, 24%) as a yellowsolid.

¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.42 (d, J=8.8 Hz, 1H), 7.09 (d, J=8.8Hz, 1H), 4.76-4.72 (m, 1H), 4.36-4.32 (m, 2H), 3.77-3.70 (m, 7H),3.23-3.16 (m, 1H), 2.94-2.74 (m, 1H), 2.76 (t, J=7.1 Hz, 2H), 2.58-2.48(m, 4H), 2.26-2.20 (m, 1H), 2.05-2.00 (m, 1H), 1.69-1.61 (m, 1H), 1.24(s, 2H), 1.14-1.09 (m, 5H). MS: (ES, m/z): 399[M+H]⁺.

The following examples in TABLE 11 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Example 247.

TABLE 11 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 248

373 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.46 (s, 1H), 7.10 (d, J = 8.4 Hz,1H), 4.81-4.78 (m, 1H), 4.19 (t, J = 6.8 Hz, 2H), 3.79 (s, 3H), 3.69 (t,J = 4.8 Hz, 4H), 3.27-3.18 (m, 1H), 3.01-2.97 (m, 1H), 2.69-2.66 (m,5H), 2.54-2.45 (m, 4H), 2.29- 2.22 (m, 1H), 1.74-1.69 (m, 1H), 1.14 (d,J = 6.7 Hz, 3H) methyl (S)-2,7-dimethyl-3-(2-morpliolinoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 249

415 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.40 (d, J = 9 Hz, 1H), 7.29 (d, J= 9 Hz, 1H), 4.73 (q, J = 6.6 Hz, 1H), 4.60-4.55 (m, 2H), 3.79-3.74 (m,7H), 3.34-3.29 (m, 1H), 2.90-2.78 (m, 3H), 2.65- 2.62 (m, 4H), 2.30-2.27(m, 1H), 1.69-1.62 (m, 10H), 1.14 (d, J = 6.6 Hz, 3H) methyl(S)-2-(tert-butyl)-7-methyl-3-(2-morpliolinoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 250

435 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.92 (d, J = 8.8 Hz, 1H), 7.77 (s,2H), 7.66-7.54 (m, 3H), 7.50 (d, J = 8.8 Hz, 1H), 4.85-4.75 (m, 3H),3.84 (s, 3H), 3.79 (d, J = 7.6 Hz, 4H), 3.18-3.14 (m, 3H), 3.08-2.96 (m,1H), 2.96-2.74 (m, 4H), 2.17-2.16 (m, 1H), 1.85-1.82 (m, 1H), 1.15 (d, J= 6.8 Hz, 3H) methyl (S)-7-methyl-3-(2-morpliolinoethyl)-2-phenyl-3,7,8,9-tetrahydro-6H-imidazo[4,5- f]quinoline-6-carboxylate 251

427 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.51 (d, J = 8.7 Hz, 1H), 7.15 (d,J = 8.7 Hz, 1H), 4.82- 4.76 (m, 1H), 4.28-4.23 (m, 2H), 3.80 (s, 3H),3.75- 3.72 (m, 4H), 3.24-2.19 (m, 1H), 3.10-2.98 (m, 3H), 2.76-2.71 (m,2H), 2.56-2.53 (m, 4H), 2.29-2.21 (m, 1H) 1.83-1.70 (m, 3H), 1.15 (d, J= 6.6 Hz, 1H), 0.83- 0.78 (m, 1H), 0.52-0.46 (m, 2H), 1.15-1.10 (m, 2H)methyl (S)-2-(2-cyclopropylethyl)-7-methyl-3-(2-morpholinoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 252

404 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.72 (d, J = 8.8 Hz, 1H), 7.48 (d,J = 8.8 Hz, 1H), 7.34- 7.26 (m, 3H), 6.88 (d, J = 6.8 Hz, 1H), 5.77-5.65(m, 2H), 4.66-4.61 (m, 1H), 3.76 (s, 3H), 2.94-2.87 (m, 1H), 2.64-2.57(m, 1H), 2.09-2.01 (m, 1H), 1.36-1.27 (m, 1H), 1.03 (d, J = 6.4 Hz, 3H)methyl (S)-3-benzyl-7-methyl-2- (trifluoromethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 253

482 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46 (d, J = 8.9 Hz, 1H), 7.41-7.25(m, 6H), 4.78- 4.72 (m, 1H), 4.42 (s, 2H), 4.06 (d, J = 7.1 Hz, 2H),3.79 (s, 3H), 3.23-3.16 (m, 1H), 3.03-2.77 (m, 5H), 2.27-2.21 (m, 1H),1.93-1.69 (m, 6H), 1.16 (d, J = 6.6 Hz, 3H) methyl(S)-2-benzyl-3-((1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 254

468 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.45 (d, J = 8.4 Hz, 1H), 7.31-7.19(m, 4H), 7.21 (d, J = 8.8 Hz, 2H), 4.83-4.80 (m, 1H), 4.47-4.28 (m, 3H),3.79 (s, 3H), 3.30-3.23 (m, 1H), 3.10-2.84 (m, 7H), 2.30-2.28 (m, 1H),1.80-1.58 (m, 3H), 1.18 (d, J = 8.8 Hz, 3H) methyl(S)-2-benzyl-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 255

443 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.44-7.41 (d, J = 13.6 Hz, 1H),7.39-7.28 (m, 6H), 4.79- 4.77 (m, 1H), 4.43 (s, 2H), 4.30 (s, 1H), 3.79(s, 3H), 3.23-3.19 (m, 1H), 3.00-2.96 (m, 1H), 2.79-2.78 (m, 1H),2.30-2.21 (m, 5H), 1.80-1.75 (m, 1H), 1.61- 1.47 (m, 4H), 1.17-1.15 (d,J = 6.4 Hz, 3H) methyl (S)-2-benzyl-3-((trans)-4-cyanocyclohexyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 256

443 ¹H-NMR (CDCl₃, 400 MHz) δ (ppm): 7.49-7.46 (m, 2H), 7.36-7.32 (m,2H), 7.28-7.26 (m, 3H), 4.80-4.78 (m, 1H), 4.43 (s, 2H), 4.33 (s, 1H),3.80 (s, 3H), 3.34-3.32 (m, 1H), 3.30-3.34 (m, 1H), 3.12-2.97 (m, 1H),2.48-2.41 (m, 2H), 2.40-2.29 (m, 1H), 2.05-2.01 (m, 2H), 1.81-1.76 (m,1H), 1.69-1.63 (m, 2H), 1.55-1.52 (m, 2H), 1.18-1.17 (d, J = 6.4 Hz, 3H)methyl (S)-2-benzyl-3-((cis)-4-cyanocyclohexyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 257

433 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.41-7.33 (m, 2H), 7.30-7.29 (m,2H), 7.25-7.21 (m, 3H), 4.84-4.79 (m, 1H), 4.45-4.31 (m, 2H), 4.07- 4.01(m, 1H), 3.80 (s, 3H), 3.35- 3.24 (m, 1H), 3.11-3.01 (m, 1H), 2.91-2.87(m, 2H), 2.47-2.43 (m, 2H), 2.34-2.25 (m, 4H), 1.93-1.71 (m, 3H),1.47-1.44 (m, 1H), 1.34-1.30 (m, 1H), 1.21 (d, J = 6.9 Hz, 3H) methyl(S)-2-benzyl-7-methyl-3-(1- methylpiperidin-4-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 258

444 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.41-7.32 (m, 1H), 7.27-7.22 (m,4H), 7.12-7.09 (m, 2H), 4.85-4.79 (m, 1H), 4.61-4.55 (m, 1H), 4.41- 4.29(m, 2H), 3.81 (s, 3H), 3.46-3.22 (m, 5H), 3.09- 2.93 (m, 3H), 2.49-2.22(m, 6H), 1.79-1.73 (m, 1H), 1.21 (d, J = 6.6 Hz, 3H) methyl(S)-2-benzyl-7-methyl-3-(2-methyl-2-azaspiro[3.3]heptan-6-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinolino-6-carboxylate 259

437 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.75-7.73 (m, 1H), 7.57-7.53 (m,2H), 7.48-7.46 (m, 1H), 6.63-6.61 (m, 1H), 6.45-6.41 (m, 1H), 5.63- 5.51(m, 2H), 5.01-4.95 (m, 1H), 4.77-4.75 (m, 1H), 4.14-4.08 (m, 2H), 3.78(s, 3H), 3.64-3.58 (m, 2H), 3.18-3.16 (m, 1H), 2.96-2.92 (m, 1H),2.59-2.52 (m, 2H), 2.26-2.23 (m, 1H), 1.76-1.68 (m, 3H), 1.14 (d, J =6.4 Hz, 3H) methyl (S)-7-methyl-2-((2-oxopyridin-1(2H)-yl)methyl)-3-(tetrahydro-2H-pyran-4-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline- 6-carboxylate 260

437 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.75-7.72 (m, 1H), 7.62-7.59 (m,2H), 7.47 (d, J = 9.0 Hz, 1H), 6.63 (d, J = 8.7 Hz, 1H), 6.44-6.43 (m,1H), 5.68-5.62 (m, 1H), 5.47-5.42 (m, 1H), 4.75-4.70 (m, 2H), 4.20-4.10(m, 1H), 4.01-3.95 (m, 1H), 4.90- 3.85 (m, 1H), 3.78 (s, 3H), 3.65-3.55(m, 1H), 3.21- 3.12 (m, 1H), 2.98-2.87 (m, 1H), 2.55-2.45 (m, 1H),2.25-2.18 (m, 1H), 1.95-1.85 (m, 3H), 1.80-1.70 (m, 1H), 1.13 (d, J =6.6 Hz, 3H) methyl (S)-7-methyl-2-((2-oxopyridin-1(2H)-yl)methyl)-3-((S)-tetrahydro-2H-pyran-3-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline- 6-carboxylate 261

487 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.51-7.46 (m, 2H), 7.41-7.35 (m,1H), 7.22 (d, J = 9 Hz, 1H), 6.59 (d, J = 9 Hz, 1H), 6.19-6.14 (m, 1H),4.84-4.80 (m, 1H), 4.45-4.38 (m, 4H), 3.81 (s, 3H), 3.46-3.39 (m, 2H),3.24-2.21 (m, 1H), 3.18-3.03 (m, 3H), 2.98 (s, 3H), 2.41-2.25 (m, 3H),1.79-1.73 (m, 1H), 1.19 (d, J = 6.6 Hz, 3H) methyl (S)-7-methyl-3-(3-(methylsulfonyl)propyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 262

472 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.56-7.54 (m, 2H), 7.44 (s, 2H),6.25-6.23 (m, 1H), 4.80-4.64 (m, 4H), 3.79 (s, 3H), 3.63-3.39 (m, 4H),3.28-3.10 (m, 3H), 3.08-2.86 (m, 3H), 2.35-2.17 (m, 1H), 2.02-1.94 (m,2H), 1.80-1.70 (m, 1H), 1.15 (d, J = 6.7 Hz, 3H) methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5- f]quinoline-6-carboxylate 263

418 ¹H-NMR (CD₃OD 300 MHz) δ (ppm): 7.45-7.22 (m, 7H), 4.78-4.73 (m,1H), 4.38 (s, 2H), 4.21-4.17 (m, 1H), 3.76 (s, 3H), 3.23-3.16 (m, 1H),2.99-2.93 (m, 1H), 2.28-2.22 (m, 1H), 2.14-2.06 (m, 2H), 1.79-1.66 (m,4H), 1.50-1.44 (m, 2H), 1.28-1.22 (m, 3H), 1.12 (d, 3H, J = 6.8 Hz)methyl (S)-2-benzyl-3-cyclohexyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline- 6-carboxylate

Examples 264 and 265: methyl(S)-2-benzyl-3-((S)-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-2-benzyl-3-((R)-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(2S)-5-amino-6-((1,1-dioxidotetrahydro-2H-thiopyran-3-yl)amino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 10-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(100 mg, 0.33 mmol, Intermediate 1) was dissolved in toluene (3 mL).Then 3-aminotetrahydro-2H-thiopyran 1,1-dioxide hydrochloride (186 mg,1.00 mmol), BrettPhos (36 mg, 0.07 mmol), 3^(rd) Generation BrettPhosprecatalyst (61 mg, 0.07 mmol) and sodium tert-butoxide (97 mg, 1.01mmol) were added. The resulting solution was stirred for 2 h at 100° C.under nitrogen atmosphere. The reaction mixture was cooled to roomtemperature and the solids were filtered out. The filtrate wasconcentrated under vacuum. The residue was subjected to purification byFCC eluting with ethyl acetate/petroleum ether (2:1). This afforded thetitle compound (54.9 mg, 45%) as a yellow solid. MS: (ES, m/z): 368[M+H]⁺.

Step 2. Synthesis of methyl(S)-2-benzyl-3-((S)-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-2-benzyl-3-((R)-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(2S)-5-amino-6-((1,1-dioxidotetrahydro-2H-thiopyran-3-yl)amino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate(54.9 mg, 0.15 mmol) was dissolved in dichloromethane (5 mL). Then2-phenylacetaldehyde (80.7 mg, 0.67 mmol) was added. The resultingsolution was stirred for 4 h at room temperature. The resulting mixturewas concentrated under vacuum. The crude product was purified byPrep-HPLC with the following conditions: Column, XBridge Shield RP18 OBDColumn, 5 μm, 19×150 mm; mobile phase, A: water (containing 10 mmol/LNH₄HCO₃) and B: ACN (30.0% to 60.0% over 7 min); UV Detector: 254 nm.The crude product was purified by Chiral-Prep-HPLC with the followingconditions (Prep-HPLC): Column, CHIRAL ART Cellulose-SB, 2×25 cm, 5 um;mobile phase, hexanes and ethanol (hold 40.0% ethanol in 30 min); UVDetector: 254 nm. This afforded the title compounds as follows: 8.9 mg(13%) of methyl(7S)-2-benzyl-3-[(3R)-1,1-dioxo-1lambda6-thian-3-yl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, first eluting isomer, RT=20.61 min) as a whitesolid and 9.0 mg (13%) of methyl(7S)-2-benzyl-3-[(3S)-1,1-dioxo-1lambda6-thian-3-yl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, second eluting isomer, RT=23.64 min) as awhite solid.

First eluting isomer: ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56 (d, J=9.0Hz, 1H), 7.46 (d, J=9.0 Hz, 1H), 7.41-7.24 (m, 5H), 4.91-4.72 (m, 2H),4.50 (d, J=16.0 Hz, 1H), 4.39 (d, J=15.9 Hz, 1H), 3.91 (t, J=12.8 Hz,1H), 3.79 (s, 3H), 3.28-3.16 (m, 2H), 3.11-2.94 (m, 3H), 2.43-2.21 (m,2H), 2.07-2.01 (m, 1H), 1.78-1.68 (m, 2H), 1.47-1.42 (m, 1H), 1.16 (d,J=6.6 Hz, 3H). MS: (ES, m/z): 468 [M+H]⁺.

Second eluting isomer: ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56 (d, J=9.0Hz, 1H), 7.46 (d, J=9.0 Hz, 1H), 7.41-7.24 (m, 5H), 4.92-4.73 (m, 2H),4.51 (d, J=15.9 Hz, 1H), 4.40 (d, J=16.0 Hz, 1H), 3.95 (t, J=12.8 Hz,1H), 3.79 (s, 3H), 3.32-3.17 (m, 2H), 3.10-2.93 (m, 3H), 2.40-2.21 (m,2H), 2.06-1.98 (m, 1H), 1.85-1.67 (m, 2H), 1.43-1.38 (m, 1H), 1.17 (d,J=6.6 Hz, 3H). MS: (ES, m/z): 468 [M+H]⁺.

The following examples in TABLE 12 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Examples 264 and 265.

TABLE 12 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 266 and 267

1^(st) eluting isomer = 472 2^(nd) eluting isomer = 472 1^(st) elutingisomer ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.61-7.49 (m, 3H), 7.44 (d, J =9.0 Hz, 1H), 6.22-6.20 (m, 1H), 4.85-4.63 (m, 4H), 3.96-3.88 (m, 1H),3.79 (s, 3H), 3.54-3.48 (m, 2H), 3.38-3.36 (m, 1H), 3.22-3.04 (m, 3H),2.96-2.88 (m, 1H), 2.50-2.32 (m, 1H), 2.34-1.97 (m, 3H), 1.83-1.60 (m,2H), 1.14 (d, J = 6.6 Hz, 3H) 2^(nd) eluting isomer ¹H-NMR (CD₃OD, 400MHz) δ (ppm): 7.61-7.49 (m, 3H), 7.44 (d, J = 9.0 Hz, 1H), 6.22-6.18 (m,1H), 4.85-4.63 (m, 4H), 3.98-3.88 (m, 1H), 3.79 (s, 3H), 3.55-3.48 (m,2H), 3.39-3.32 (m, 1H), 3.28-3.07 (m, 3H), 2.97-2.87 (m, 1H), 2.54-2.36(m, 1H), 2.35-1.98 (m, 3H), 1.80-1.64 (m, 2H), 1.15 (d, J = 6.6 Hz, 3H)methyl (7S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(1,1-dioxidotetrahydro-2H-thiopyran-3-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 268 and 269

1^(st) eluting isomer = 473 2^(nd) eluting isomer = 473 1^(st) elutingisomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.56-7.53 (m, 3H), 7.19 (d, J =9 Hz, 1H), 5.11-5.07 (m, 2H), 4.92-4.75 (m, 2H), 3.80-3.79 (m, 4H),3.76-3.66 (m, 2H), 3.24-3.13 (m, 3H), 3.10-2.99 (m, 2H), 2.40- 2.15 (m,4H), 2.02-1.98 (m, 1H), 1.80-1.71 (m, 1H), 1.15 (d, J = 6.6 Hz, 3H)2^(nd) eluting isomer ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.53-7.52 (m,2H), 7.50-7.48 (m, 1H), 7.18 (d, J = 9 Hz, 1H), 5.11-5.04 (m, 2H),4.88-4.76 (m, 2H), 3.82-3.73 (m, 4H), 3.67-3.62 (m, 2H), 3.22-3.09 (m,3H), 3.05- 2.96 (m, 2H), 2.28-2.15 (m, 4H), 2.08-2.04 (m, 1H), 1.77-1.70(m, 1H), 1.15 (d, J = 6.9 Hz, 3H) methyl (7S)-2-(2-(2H-1,2,3-triazol-2-yl)ethyl)-3-(1,1-dioxidotetrahydro-2H- thiopyran-3-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 270

460 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.50-7.49 (m, 2H), 7.28-7.26 (m,1H), 7.15 (d, J = 9.0 Hz, 1H), 6.12-6.11 (m, 1H), 4.81-4.77 (m, 3H),4.13-4.09 (m, 2H), 3.78 (s, 3H), 3.51-3.50 (m, 2H), 3.27-3.19 (m, 1H),3.06-3.00 (m, 1H), 2.92-2.89 (m, 5H), 2.29-2.14 (m, 3H), 1.80-1.72 (m,1H), 1.15 (d, J = 6.6 Hz, 3H) methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(3-(methylsulfonyl)propyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5- f]quinoline-6-carboxylate 271

446 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.52-7.51 (m, 2H), 7.27-7.26 (m,1H), 7.13 (d, J = 8.7 Hz, 1H), 6.14-6.12 (m, 1H), 4.82-4.76 (m, 3H),4.40-4.35 (m, 2H), 3.79 (s, 3H), 3.54-3.48 (m, 2H), 3.28-3.17 (m, 3H),3.04-2.97 (m, 1H), 2.74 (s, 3H), 2.30-2.19 (m, 1H), 1.79- 1.70 (m, 1H),1.15 (d, J = 6.6 Hz, 3H) methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(methylsulfonyl)ethyl)- 3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 272

480 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.48-7.41 (m, 2H), 7.36-7.30 (m,1H), 7.12 (d, J = 9.0 Hz, 1H), 6.56 (d, J = 9.0 Hz, 1H), 6.11-6.07 (m,1H), 4.83-4.77 (m, 1H), 4.48-4.36 (m, 2H), 4.23-4.18 (m, 2H), 3.78 (s,3H), 3.65-3.63 (m, 4H), 3.44-3.42 (m, 2H), 3.22-3.17 (m, 1H), 3.05-2.97(m, 1H), 2.65-2.61 (m, 2H), 2.48-2.45 (m, 4H), 2.27-2.22 (m, 1H),1.77-1.70 (m, 1H), 1.15 (d, J = 6.6 Hz, 3H) methyl (S)-7-methyl-3-(2-morpholinoethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 273

473 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.52-7.43 (m, 1H), 7.41-7.35 (m,2H), 7.23-7.20 (m, 1H), 6.60-6.57 (d, J = 9 Hz, 1H), 6.20-6.15 (m, 1H),4.83-4.73 (m, 3H), 4.41-4.33 (m, 2H), 3.81 (s, 3H), 3.58-3.53 (m, 2H),3.48-3.42 (m, 2H), 3.22-3.18 (m, 1H), 3.03-2.97 (m, 4H), 2.31-2.27 (m,1H), 1.78-1.71 (m, 1H), 1.18 (d, J = 6.6 Hz, 3H) methyl(S)-7-methyl-3-(2- (methylsulfonyl)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate 274

450 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.52-7.51 (m, 2H), 7.27-7.26 (m,1H), 7.13 (d, J = 8.7 Hz, 1H), 6.14-6.12 (m, 1H), 4.82-4.76 (m, 3H),4.40-4.35 (m, 2H), 3.79 (s, 3H), 3.54-3.48 (m, 2H), 3.28-3.17 (m, 3H),3.04-2.97 (m, 1H), 2.74 (s, 3H), 2.30-2.19 (m, 1H), 1.79-1.70 (m, 1H),1.15 (d, J = 6.6 Hz, 3H) methyl (S)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3-((R)-tetrahydro-2H- pyran-3-yl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 275

473 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.69 (s, 2H), 7.42-7.38 (m, 2H),5.01-4.96 (m, 2H), 4.87- 4.70 (m, 2H), 3.79 (s, 3H), 3.70-3.63 (m, 2H),3.59-3.43 (m, 2H), 3.28-2.81 (m, 6H), 2.26-2.10 (m, 3H), 1.81- 1.64 (m,1H), 1.13 (d, J = 6.7 Hz, 3H) methyl (S)-2-(2-(2H-1,2,3-triazol-2-yl)ethyl)-3-(1,1-dioxidotetrahydro-2H- thiopyran-4-yl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6- carboxylate

Examples 276: methyl(S)-3-((R)-1-(1H-tetrazol-5-yl)piperidin-3-yl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(2S)-5-amino-6-[[(3R)-1-[(tert-butoxy)carbonyl]piperidin-3-yl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 50-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(400 mg, 1.34 mmol, Intermediate 1) was dissolved in dioxane (10 mL).Then tert-butyl (3R)-3-aminopiperidine-1-carboxylate (800 mg, 3.99mmol), BrettPhos (288 mg, 0.54 mmol), BrettPhos Pd 3^(rd) generationprecatalyst (243 mg, 0.27 mmol) and sodium tert-butoxide (386 mg, 4.02mmol) were added. The resulting solution was stirred for 2 h at 100° C.in the nitrogen atmosphere. The reaction mixture was cooled and theresulting solids were filtered out. The filtrate was concentrated undervacuum. The residue was subjected to purification by FCC eluting withethyl acetate/petroleum ether (2:1). This afforded the title compound(300 mg, 54%) as a green solid. MS: (ES, m/z): 420 [M+H]⁺.

Step 2. Synthesis of tert-butyl(3R)-3-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]piperidine-1-carboxylate

Into a 50-mL round-bottom flask, methyl(2S)-5-amino-6-[[(3R)-1-[(tert-butoxy)carbonyl]piperidin-3-yl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(300 mg, 0.72 mmol) was dissolved in dichloromethane (10 mL). Then2-phenylacetaldehyde (258 mg, 2.15 mmol) was added. The resultingsolution was stirred for 2 h at room temperature. The resulting mixturewas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (2:1). This affordedthe title compound (200 mg, 54%) as a green solid. MS: (ES, m/z): 519[M+H]⁺.

Step 3. Synthesis of methyl(7S)-2-benzyl-7-methyl-3-[(3R)-piperidin-3-yl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 10-mL round-bottom flask, tert-butyl(3R)-3-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]piperidine-1-carboxylate(200 mg, 0.39 mmol) was dissolved in dichloromethane (3 mL). Thentrifluoroacetic acid (1 mL) was added. The flask was wrapped withaluminum foil and the resulting solution was stirred for 1 h at roomtemperature. The resulting mixture was concentrated under vacuum. Afteraddition of water, the pH value of the mixture was adjusted to 8-9 withsodium bicarbonate. The resulting solution was extracted with 2×10 mL ofdichloromethane. The organic layers were combined, dried over sodiumsulfate, filtered and concentrated. The residue was subjected topurification by FCC eluting with ethyl acetate/petroleum ether (3:1).This afforded the title compound (140 mg, 87%) as a green solid. MS:(ES, m/z): 419 [M+H]⁺.

Step 4. Synthesis of methyl(7S)-3-[(3R)-1-[(2H-1,2,3-benzotriazol-2-yl)carboximidoyl]piperidin-3-yl]-2-benzyl-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(7S)-2-benzyl-7-methyl-3-[(3R)-piperidin-3-yl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(50 mg, 0.12 mmol) was dissolved in dichloromethane (5 mL). Then2-[(2H-1,2,3-benzotriazol-2-yl)carboximidoyl]-2H-1,2,3-benzotriazole(31.45 mg, 0.12 mmol) was added. The resulting solution was stirred for3 days at room temperature. The resulting mixture was concentrated undervacuum and this afforded the title compound (60 mg, crude) as greencrude oil, which could be used into next step without furtherpurification. MS: (ES, m/z): 563 [M+H]⁺.

Step 5. Synthesis of methyl(7S)-2-benzyl-7-methyl-3-[(3R)-1-(1H-1,2,3,4-tetrazol-5-yl)piperidin-3-yl]-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(7S)-3-[(3R)-1-[(2H-1,2,3-benzotriazol-2-yl)carboximidoyl]piperidin-3-yl]-2-benzyl-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(60 mg, 0.11 mmol) was dissolved in dichloromethane (5 mL). Then sodiumazide (7.62 mg, 0.12 mmol) was added, followed by acetic acid (0.1 mL).The resulting solution was stirred for 1 day at room temperature. Theresulting mixture was concentrated under vacuum. After addition ofwater, the pH value of the reaction mixture was adjusted to 9-10 withsodium bicarbonate. The resulting solution was extracted with 2×5 mL ofdichloromethane. The organic layers were combined, dried over sodiumsulfate, filtered and concentrated. The crude product was purified byPrep-HPLC with the following conditions: Column, XBridge C18 OBD PrepColumn, 5 um, 19 mm×150 mm; mobile phase, A: Water (containing 10 mmol/LNH₄HCO₃) and B: ACN (30.0% to 50.0% ACN over 7 min); UV Detector: 254nm. This afforded the title compound (9.3 mg, 18%) of as a white solid.¹H-NMR: (300 MHz, CD₃CD, ppm): 7.57-7.54 (d, J=9 Hz, 1H), 7.46-7.43 (d,J=9 Hz, 1H), 7.18-7.30 (m, 5H), 4.86-4.80 (m, 1H), 4.47-4.45 (m, 3H),3.82-3.76 (m, 6H), 3.30-3.11 (m, 2H), 3.05-2.96 (m, 1H),2.43-2.23 (m,2H), 1.85-1.73 (m, 2H), 1.61-1.46 (m, 2H), 1.18-1.16 (d, J=6.6 Hz, 3H).MS: (ES, m/z): 487 [M+H]⁺.

The following examples in TABLE 13 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Examples 276.

TABLE 13 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 277

487 ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.57-7.54 (d, J = 9 Hz, 1H),7.46-7.43 (d, J = 9 Hz, 1H), 7.18-7.30 (m, 5H), 4.83-4.77 (m, 1H),4.52-4.40 (m, 3H), 3.92-3.79 (m, 6H), 3.29-3.15 (m, 2H), 3.04-2.95 (m,1H), 2.35-2.23 (m, 2H), 1.85-1.76 (m, 2H), 1.57-1.48 (m, 2H), 1.19-1.17(d, J = 6.9 Hz, 3H) methyl (S)-3-((S)-1-(1H-tetrazol-5-yl)piperidin-3-yl)-2-benzyl-7-methyl- 3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 278

487 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.38-7.21 (m, 7H), 4.78-4.74 (m,1H), 4.55-4.42 (m, 3H), 3.97-3.93 (m, 2H), 3.75 (s, 3H), 3.26-3.16 (m,1H), 3.03- 2.92 (m, 3H), 2.48-2.40 (m, 2H), 2.26-2.21 (m, 1H), 1.81-1.70(m, 1H), 1.55-1.42 (m, 2H), 1.13 (d, J = 6.8 Hz, 3H). methyl(S)-3-(1-(1H-tetrazol-5- yl)piperidin-4-yl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5- f]quinoline-6-carboxylate

Examples 279 and 280: methyl(S)-3-((1R,3S)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-3-((1S,3R)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(S)-5-amino-6-(((cis)-3-cyanocyclohexyl)amino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 50-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, was placed cis-3-aminocyclohexane-1-carbonitrilehydrochloride (714 mg, 4.00 mmol, Intermediate 29), NaOtBu (642 mg, 6.35mmol), methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(443 mg, 1.33 mmol, Intermediate 1), Brettphos (539 mg, 0.95 mmol), andBrettPhos Pd 3^(rd) generation precatalyst (269.5 mg, 0.28 mmol) indioxane (10 mL). The resulting suspension was stirred for 2 h at 100° C.in an oil bath. The reaction mixture was cooled to room temperature. Thesolids were filtered out. The resulting mixture was concentrated undervacuum. The residue was subjected to FCC eluting with ethylacetate/petroleum ether (1/1). This afforded the title compound (250 mg,47%) as a green solid. MS: (ES, m/z): 343 [M+H]⁺.

Step 2. Synthesis of methyl(S)-2-benzyl-3-((cis)-3-cyanocyclohexyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 50-mL round-bottom flask, was placed methyl(S)-5-amino-6-(((cis)-3-cyanocyclohexyl)amino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate(250 mg, 0.66 mmol), and 2-phenylacetaldehyde (263 mg, 2.08 mmol) indichloromethane (5 mL). The resulting solution was stirred overnight atrt. The resulting mixture was concentrated under vacuum. The residue wassubjected to FCC eluting with ethyl acetate/petroleum ether (2/1). Thisafforded the title compound (256 mg, 79%) as a light yellow solid. MS:(ES, m/z): 443 [M+H]⁺.

Step 3. Synthesis of methyl(S)-3-((1R,3S)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-3-((1S,3R)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 20-mL sealed tube, was placed methyl(7S)-2-benzyl-3-(3-cyanocyclohexyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(256.0 mg, 0.52 mmol), sodium azide (213 mg, 3.12 mmol) and NH₄Cl (175mg, 3.12 mmol) in N,N-dimethylformamide (8 mL). The final reactionmixture was irradiated with microwave radiation for 3 h at 140° C. Thereaction mixture was cooled to room temperature. The reaction was thenquenched by the addition of 10 mL of saturated sodium bicarbonate. Theresulting solution was extracted with 3×10 mL of ethyl acetate and theorganic layers combined and dried over anhydrous sodium sulfate andconcentrated under vacuum. The crude products were purified by Prep-HPLCwith the following conditions: Column, XSelect CSH Prep C18 OBD Column,19×250 mm,5 um; mobile phase, Water (10 mmol/L NH₄HCO₃) and ACN (2.0%ACN up to 40.0% in 14 min); Detector, UV 254 nm.

This afforded the title compounds as follows: 22.6 mg (9%) of methyl(S)-3-((1R,3S)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, first eluting isomer) as a white solid, and47.0 mg (18%) of methyl(S)-3-((1S,3R)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, second eluting isomer) as a white solid.

First eluting isomer: ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.63-7.49 (m,1H), 7.49-7.34 (m, 1H), 7.34-7.16 (m, 5H), 4.86-4.68 (m, 1H), 4.57-4.32(m, 3H), 3.77 (s, 3H), 3.28-2.89 (m, 3H), 2.64-2.33 (m, 1H), 2.33-1.39(m, 9H), 1.15 (d, J=6.6 Hz, 3H). MS: (ES, m/z): 486 [M+H]⁺.

Second eluting isomer: ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.63-7.49 (m,1H), 7.48-7.36 (m, 1H), 7.36-7.16 (m, 5H), 4.83-4.70 (m, 1H), 4.57-4.38(m, 3H), 3.76 (s, 3H), 3.20-2.89 (m, 3H), 2.63-2.47 (m, 1H), 2.32-1.99(m, 3H), 1.99-1.82 (m, 2H), 1.82-1.40 (m, 4H), 1.16 (d, J=6.6 Hz, 3H).MS: (ES, m/z): 486 [M+H]⁺.

Examples 281 and 282: methyl(S)-3-((1R,3R)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-3-((1S,3S)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(S)-5-amino-6-(((trans)-3-cyanocyclohexyl)amino)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Into a 25-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, was placed(trans)-3-aminocyclohexane-1-carbonitrile (134 mg, 1.03 mmol), NaOtBu(130 mg, 1.29 mmol), methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydronaphthalene-1-carboxylate(100 mg, 0.30 mmol, Intermediate 1), Brettphos (72 mg, 0.13 mmol), andBrettPhos Pd G3 precatalyst (60 mg, 0.06 mmol) in dioxane (5 mL). Theresulting solution was stirred for 1 h at 100° C. in an oil bath. Thereaction mixture was cooled to room temperature. The solids werefiltered out. The resulting mixture was concentrated under vacuum. Theresidue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (1:1). This afforded the title compound (60 mg,47%) as a dark green solid. MS: (ES, m/z): 343 [M+H]⁺.

Step 2. Synthesis of methyl(S)-2-benzyl-3-((trans)-3-cyanocyclohexyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, was placed methyl(2S)-5-amino-6-[[(trans)-3-cyanocyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(60 mg, 0.15 mmol), and 2-phenylacetaldehyde (63 mg, 0.50 mmol) indichloromethane (2 mL). The resulting solution was stirred for 1 h atrt. The resulting mixture was concentrated under vacuum. The residue wassubjected to purification by FCC eluting with ethyl acetate/petroleumether (0%-40%). This afforded the title compound (50 mg, 68%) as ayellow oil. MS: (ES, m/z): 443 [M+H]⁺.

Step 3. Synthesis of methyl(S)-3-((1R,3R)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylateand methyl(S)-3-((1S,3S)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 20-mL sealed tube, was placed methyl(S)-2-benzyl-3-((trans)-3-cyanocyclohexyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate(256.0 mg, 0.52 mmol), NH₄Cl (175 mg, 3.12 mmol) and NaN₃ (213 mg, 3.12mmol) in N,N-dimethylformamide (8 mL). The final reaction mixture wasirradiated with microwave radiation for 3 h at 140° C. The reactionmixture was cooled to room temperature. The reaction was then quenchedby the addition of 10 mL of saturated sodium bicarbonate. The resultingsolution was extracted with 3×10 mL of ethyl acetate and the organiclayers combined, dried over anhydrous sodium sulfate and concentratedunder vacuum. The crude products were purified by Prep-HPLC with thefollowing conditions: Column, XBridge C18 OBD Prep Column, 100 Å, 10 um,19 mm×250 mm; mobile phase, Water (10 mmol/L NH₄HCO₃) and ACN (20.0% ACNup to 40.0% in 7 min); Detector, UV 254/220 nm.

This afforded the title compounds as follows: 9.8 mg (19%) of methyl(S)-3-((1R,3R)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, first eluting isomer) as a white solid, 2.1 mg(4%) of methyl(S)-3-((1S,3S)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate(assumed stereochemistry, second eluting isomer) as a white solid.

First eluting isomer: ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.57-7.44 (m,1H), 7.42-7.31 (m, 1H), 7.19-7.04 (m, 3H), 7.01-7.6.82 (m, 2H),4.81-4.72 (m, 1H), 4.62-4.43 (m, 1H), 4.41-4.19 (m, 2H), 3.77 (s, 3H),3.59-2.46 (m, 1H), 3.27-3.13 (m, 1H), 3.04-2.88 (m, 1H), 2.71-2.42 (m,2H), 2.42-2.03 (m, 3H), 1.97-1.63 (m, 2H), 1.62-1.44 (m, 1H), 1.32-1.22(m, 1H), 1.15 (d, J=6.9 Hz, 3H), 1.04-0.91 (m, 1H). MS: (ES, m/z): 486[M+H]⁺.

Second eluting isomer: ¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53-7.41 (m,1H), 7.41-7.29 (m, 1H), 7.18-7.03 (m, 3H), 6.99-6.82 (m, 2H), 4.82-4.67(m, 1H), 4.62-4.41 (m, 1H), 4.41-4.18 (m, 2H), 3.77 (s, 3H),3.58-2.47(m, 1H), 3.25-3.13 (m, 1H), 3.01-2.87 (m, 1H), 2.76-2.42 (m, 2H),2.42-2.94 (m, 3H), 1.87-1.68 (m, 2H), 1.57-1.41 (m, 1H), 1.37-1.22 (m,1H), 1.16 (d, J=6.9 Hz, 3H), 1.03-0.89 (m, 1H). MS: (ES, m/z): 486[M+H]⁺.

The following examples in TABLE 14 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Examples 281 and 282.

TABLE 14 LRMS Example m/z Number Structure and Compound Name [M + H]⁺¹HNMR 283

486 ¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.60-7.56 (d, J = 9 Hz, 1H),7.32-7.22 (m, 6H), 4.86-4.80 (m, 1H), 4.47-4.31 (m, 2H), 4.04-4.10 (m,1H), 3.88 (s, 3H), 3.32-3.22 (m, 1H), 3.10-2.95 (m, 2H), 2.28-2.07 (m,6H), 1.78-1.69 (m, 4H), 1.22-1.19 (d, J = 6.6 Hz, 3H) methyl(S)-3-((trans)-4-(1H-tetrazol-5- yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5- f]quinoline-6-carboxylate 284

486 ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.35-7.23 (m, 6H), 7.19-7.17 (d, J= 9.2 Hz, 1H), 4.77-4.72 (m, 1H), 4.41-4.38 (m, 3H), 3.75 (s, 3H),3.31-3.30 (m, 1H), 3.21-3.15 (m, 1H), 2.97-2.91 (m, 1H), 2.45-2.41 (m,2H), 2.26-2.21 (m, 3H), 1.88-1.71 (m, 3H), 1.40-1.28 (m, 2H), 1.13-1.12(d, J = 9.2 Hz, 3H) methyl (S)-3-((cis)-4-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl- 3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Example 285:(S)-2-(2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)aceticacid

Into a 50-mL round-bottom flask, methyl(7S)-2-benzyl-7-methyl-3-(2-oxoethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(60 mg, 0.16 mmol) was dissolved in tetrahydrofuran (2 mL). Then sodiumdihydrogen orthophosphate (191 mg, 1.59 mmol), dimethyl sulfoxide (3 mL)and water (2 mL) were added, followed by a solution of sodium chlorite(143 mg, 1.26 mmol, 80%) in water (1 mL) dropwise. The resultingsolution was stirred for 12 h at room temperature. The resultingsolution was diluted with 20 mL of water and extracted with 2×30 mL ofethyl acetate. The organic layers were combined, dried over sodiumsulfate, filtered and concentrated under vacuum. The crude product waspurified with the following conditions: Column, XBridge Prep C18 OBDColumn, 100 Å, 5 μm, 19 mm×250 mm; Mobile Phase, A: water (containing0.1% FA) and B: ACN (20% to 37% ACN over 8 min); UV Detector: 254 nm.This afforded the title compound (5.7 mg, 9%) as a white solid. ¹H-NMR(DMSO-d6, 400 MHz,) δ(ppm): 13.14 (s, 1H), 7.33-7.24 (m, 5H), 7.24-7.16(m, 2H), 4.98 (d, J=2.4 Hz, 2H), 4.66-4.62 (m, J=6.0 Hz, 1H), 4.24 (s,2H), 3.66 (s, 3H), 3.11-3.01 (m, 1H), 2.84-2.77 (m, 1H), 2.20-2.09 (m,1H), 1.66-1.56 (m, 1H), 1.06 (d, J=7.2 Hz, 3H). MS: (ES, m/z): 394[M+H]⁺.

Example 286: methyl(S)-3-(2-amino-2-oxoethyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 100-mL round-bottom flask, ammonium chloride (90 mg, 1.68 mmol)was dissolved in methanol (20 mL). Then triethylamine (72 mg, 0.71mmol), 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methyl morpholiniumchloride (351 mg, 1.27 mmol) and2-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H, 6H, 7H, 8H,9H-imidazo[4, 5-f]quinolin-3-yl]acetic acid (130 mg, 0.33 mmol) wereadded. The resulting solution was stirred for 16 h at room temperature.The resulting solution was diluted with 100 mL of water and extractedwith 3×50 mL of dichloromethane. The organic layers were combined, driedover anhydrous sodium sulfate, filtered and concentrated under vacuum.The crude product was purified by Prep-HPLC with the followingconditions: Column, XBridge C18 OBD Prep Column, 100 Å, 5 μm, 19 mm×250mm; mobile phase, A: water (10 mmol/L NH₄HCO₃) and B: ACN (30.0% to60.0% ACN over 8 min); UV Detector: 254 nm. This afforded the titlecompound (8.6 mg, 7%) as a white solid. ¹H NMR (300 MHz, DMSO-d₆) δ 7.68(s, 1H), 7.36-7.17 (m, 7H), 7.13 (d, J=9.0 Hz, 1H), 4.73 (s, 2H),4.69-4.56 (m, 1H), 4.19 (s, 2H), 3.64 (s, 3H), 3.11-2.96 (m, 1H),2.84-2.67 (m, 1H), 2.21-2.04 (m, 1H), 1.65-1.52 (m, 1H), 1.04 (d, J=6.6Hz, 3H). MS: (ES, m/z): 393 [M+H]⁺.

Example 287: methyl(S)-2-benzyl-3-(2-hydroxyethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(7S)-2-benzyl-7-methyl-3-(2-oxoethyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(100 mg, 0.26 mmol) was dissolved in tetrahydrofuran (5 mL). Then sodiumborohydride (11 mg, 0.30 mmol) was added. The resulting solution wasstirred for 2 h at 0° C. in a water/ice bath. The resulting solution wasdiluted with 50 mL of water and extracted with 3×50 mL of ethyl acetate.The organic layers were combined, dried over anhydrous sodium sulfate,filtered and concentrated under vacuum. The crude product was purifiedby Prep-HPLC with the following conditions: Column, XBridge Prep C18 OBDColumn, 19×150 mm 5 μm; mobile phase, A: Water (containing 10 mmol/LNH₄HCO₃) and B: ACN (5.0% to 55.0% ACN over 7 min); UV Detector: 254 nm.This afforded the title compound (3.1 mg, 3%) as a white solid. ¹H NMR(300 MHz, CDCl₃) δ(ppm): 7.45-7.42 (m, 1H), 7.34-7.22 (m, 3H), 7.22-7.15(m, 2H), 7.13-7.11 (m, 1H), 4.82-4.76 (m, 1H), 4.42-4.31 (m, 2H),4.12-4.08 (m, 2H), 3.78-3.72 (m, 5H), 3.29-3.18 (m, 1H), 3.03-2.93 (m,1H), 2.39-2.32 (s, 1H), 2.30-2.20 (m, 1H), 1.77-1.75 (m, 1H), 1.15 (d,J=6.6 Hz, 3H). MS: (ES, m/z): 380 [M+H]⁺.

Example 288:(S)-3-(2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)propanoicacid

Step 1. Synthesis of methyl(2S)-5-amino-6-[(3,3-diethoxypropyl)amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

Into a 25-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, methyl(2S)-5-amino-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(300 mg, 1.00 mmol, Intermediate 1) was dissolved in toluene (5 mL).Then 3,3-diethoxypropan-1-amine (885 mg, 6.01 mmol), 3^(rd) GenerationBrettPhos precatalyst (91 mg, 0.10 mmol), BrettPhos (108 mg, 0.20 mmol)and sodium tert-butoxide (289 mg, 3.01 mmol) were added successively.The resulting solution was stirred for 2 h at 110° C. under nitrogenatmosphere. The reaction mixture was cooled and the resulting solidswere filtered out. The filtrate was concentrated under vacuum. Theresidue was subjected to purification by FCC eluting with ethylacetate/petroleum ether (2:1). This afforded the title compound (240 mg,62%) as a yellow oil. MS: (ES, m/z): 366 [M+H]⁺.

Step 2. Synthesis of methyl(7S)-2-benzyl-3-(3,3-diethoxypropyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(2S)-5-amino-6-[(3,3-diethoxypropyl)amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(240 mg, 0.66 mmol) was dissolved in toluene (3 mL). Then2-phenylacetaldehyde (158 mg, 1.32 mmol) was added. The resultingsolution was stirred for 14 h at room temperature. The resulting mixturewas concentrated under vacuum. The residue was subjected to purificationby FCC eluting with ethyl acetate/petroleum ether (1:1). This affordedthe title compound (220 mg, 72%) as a yellow oil. MS: (ES, m/z): 466[M+H]⁺.

Step 3. Synthesis of methyl(7S)-2-benzyl-7-methyl-3-(3-oxopropyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 25-mL round-bottom flask, methyl(7S)-2-benzyl-3-(3,3-diethoxypropyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(220 mg, 0.47 mmol) was dissolved in tetrahydrofuran (3 mL). Thenhydrochloric acid (aq, 4 M, 6 mL) was added. The resulting solution wasstirred for 3 h at 60° C. After cooled to room temperature, water wasadded. The resulting solution was extracted with 3×20 mL of ethylacetate. The organic layers were combined, dried over anhydrous sodiumsulfate, filtered and concentrated under vacuum. This afforded the titlecompound (140 mg, crude) as a yellow oil. MS: (ES, m/z): 392 [M+H]⁺.

Step 4. Synthesis of(S)-3-(2-benzyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)propanoicacid

Into a 10-mL round-bottom flask, methyl(7S)-2-benzyl-7-methyl-3-(3-oxopropyl)-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(50 mg, 0.13 mmol) was dissolved in tetrahydrofuran (1 mL). Then sodiumchlorite (57.5 mg, 0.64 mmol), sodium dihydrogen orthophosphate (76 mg,0.63 mmol), dimethyl sulfoxide (1 mL) and water (1 mL) were addedsuccessively. The resulting solution was stirred for 2 h at roomtemperature. The resulting solution was added 20 ml of water andextracted with 3×20 mL of ethyl acetate. The organic layers werecombined, dried over anhydrous sodium sulfate, filtered and concentratedunder vacuum. The crude product was purified by Prep-HPLC with thefollowing conditions: Column, XBridge C18 OBD Prep Column, 100 Å, 5 μm,19 mm×250 mm; mobile phase, A: Water (containing 10 mmol/L NH₄HCO₃) andB: ACN (20.0% to 40.0% ACN over 8 min); UV Detector: 254 nm. Thisafforded the title compound (5.4 mg, 10%) as a white solid. ¹H-NMR(CDCl₃, 300 MHz) δ (ppm): 7.51 (d, J=8.1 Hz, 1H), 7.19-7.11 (m, 6H),4.82-4.76 (m, 1H), 4.53-4.48 (m, 2H), 4.35-4.17 (s, 2H), 3.77 (s, 3H),3.22-3.14 (m, 1H), 3.02-2.96 (m, 1H), 2.63-2.59 (m, 2H), 2.21-2.19 (m,1H), 1.76-1.70 (m, 1H), 1.13 (d, J=6.3 Hz, 3H). MS: (ES, m/z): 408[M+H]⁺.

Example 289: methyl(7S)-2-benzyl-3-(2-carbamoylethyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

Into a 10-mL round-bottom flask,3-[(7S)-2-benzyl-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]propanoicacid (50 mg, 0.12 mmol) was dissolved in methanol (2 mL). Then ammoniumchloride (53.5 mg, 1.00 mmol), triethylamine (10 mg, 0.10 mmol) and4-(4,6-dimethoxy-1,3,5-triazine-2-yl)-4-methyl morpholinium chloride(43.6 mg, 0.16 mmol) were added successively. The resulting solution wasstirred for 12 h at room temperature. The solids were filtered out andthe filtrate was concentrated under vacuum. The crude product waspurified by Prep-HPLC with the following conditions (2#-AnalyseHPLC-SHIMADZU): Column, XBridge C18 OBD Prep Column, 100 Å, 5 um, 19mm×250 mm; mobile phase, A: Water (containing 10 mmol/L NH₄HCO₃) and B:ACN (30.0% to 45.0% ACN over 8 min); UV Detector: 254 nm. This affordedthe title compound (2.4 mg, 5%) as a white solid. ¹H-NMR (CDCl₃, 300MHz) δ (ppm): 7.46 (d, J=9.0 Hz, 1H), 7.33-7.29 (m, 4H), 7.24-7.22 (m,1H), 7.12 (d, J=8.7 Hz, 1H), 5.19-5.12 (m, 2H), 4.82-4.77 (m, 1H),4.50-4.29 (m, 4H), 3.78 (s, 3H), 3.31-3.22 (m, 1H), 3.09-2.99 (m, 1H),2.32-2.17 (m, 3H), 1.79-1.71 (m, 1H), 1.16 (d, J=6.6 Hz, 3H). MS: (ES,m/z): 407 [M+H]⁺.

Example 290: methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(((1-methyl-11H-pyrazol-3-yl)methyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

To a solution of methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2,2-dimethoxyethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate(726 mg, 1.698 mmol) in THE (4.2 mL), was added HCl aqueous solution (4M, 4.2 mL, 16.98 mmol). The mixture was heated at 60° C. for 4 h. Afterbeing cooled to rt, The mixture was basified with saturated sodiumbicarbonate, and extracted with ethyl acetate. The combined organiclayers were dried over sodium sulfate, filtered and concentrated. 680.2mg of methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylatewas obtained (1.78 mmol, 105% yield). MS (ES, m/z): 400 (M+H₂O+1) and414 (M+MeOH+1). The crude product was used for next step without furtherpurification.

Step 2. Synthesis of methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(((1-methyl-11H-pyrazol-3-yl)methyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

To a solution of methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate(0.2 M in 1,4-dioxane with 10% HOAc, 100 μL, 0.02 mmol), was added(1-methyl-1H-pyrazol-3-yl)methanamine (1 M 1,4-dioxane, 200 μL, 0.2mmol). The resulting mixture was put on a shaker at rt for 30 min beforea solution of sodium triacetoxyborohydride (0.2 M in 1,2-DCE, 200 μL,0.04 mmol) was added. The mixture was then put on a shaker at rt for 20h. The mixture was diluted with ethyl acetate (0.8 mL) and 1N NaOH inbrine (0.45 mL). the organic layer was separated. The aqueous layer wasextracted with ethyl acetate (0.8 mL) one more time. The combinedorganic layers were dried down and the residue was purified by HPLC:Water Autopurification MS-directed HPLC prep fraction collection withthe following conditions Column, Waters XBridge OBD C18, 5 um, 19×50 mm;flow rate 20 ml/min; mobile phase, water with 0.1% ammonium hydroxide(A) and methanol with 0.1% ammonium hydroxide (B) running the followinggradient 0 to 2 mins (15% B), 2 to 6 mins (15-100% B); Detector ZQ MassDetector in electrospray ionization mode. This provided 6.1 mg of methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(((1-methyl-1H-pyrazol-3-yl)methyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate(12.8 μmol, 64% yield) was obtained. MS (ESI, pos. ion) m/z: 477 (M+1).

The following examples in TABLE 15 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Example 290.

TABLE 15 LRMS Example m/z Number Structure and Compound Name [M + H]⁺291

464 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((isoxazol-5-ylmethyl)amino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 292

464 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-((oxazol-5-ylmethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 293

477 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(((1-methyl-1H-pyrazol-4-yl)methyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 294

474 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-((pyridin-3-ylmethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 295

495 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)amino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 296

441 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((2-hydroxyethyl)(methyl)amino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 297

482 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((2-(dimethylamino)-2-oxoethyl)(methyl)amino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 298

467 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(4-hydroxypiperidin-1-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 299

481 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(4-(hydroxymethyl)piperidin-1-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 300

494 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-((2-oxo-2-(pyrrolidin-1-yl)ethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 301

481 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(methyl(tetrahydro-2H-pyran-4-yl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 302

467 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(methyl((S)-tetrahydrofuran-3-yl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 303

480 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((S)-3-carbamoylprrolidin-1-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 304

469 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((2-hydroxy-2-methylpropyl)(methyl)amino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 305

439 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(oxetan-3-ylamino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 306

436 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((2-cyanoethyl)amino)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 307

495 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-((2-(2-oxoimidazolidin-1-yl)ethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 308

476 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(4-cyanopiperidin-1-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 309

494 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((R)-3-acetamidopyrrolidin-1-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 310

494 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((S)-3-acetamidopyrrolidin-1-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 311

494 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(4-isopropylpiperazin-1-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 312

492 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(4-cyclopropylpiperazin-1-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 313

496 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(4-(2-hydroxyethyl)pipeiazin-1-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 314

502 methyl (S)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3-(2-((pyrimidin-4-ylmethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 315

504 methyl (S)-7-methyl-3-(2-(((1-methyl-1H-pyrazol-4-yl)methyl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 316

504 methyl (S)-7-methyl-3-(2-(((1-methyl-1H-pyrazol-3-yl)methyl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 317

505 methyl (S)-7-methyl-3-(2-(((1-methyl-1H-1,2,4-triazol-5-yl)methyl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 318

501 methyl (S)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3-(2-((pyridin-3-ylmethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 319

494 methyl (S)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3-(2-((((R)-tetrahydrofuran-2-yl)methyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 320

436 methyl (S)-3-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)amino)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 321

495 methyl (S)-3-(2-(((R)-1-hydroxypropan-2-yl)amino)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetratydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 322

476 methyl (S)-3-(2-((2-(dimethylamino)-2-oxoethyl)(methyl)amino)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 323

494 methyl (S)-3-(2-(4-(hydroxymethyl)piperidin-1-yl)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 324

521 methyl (S)-3-(2-((2-(dimethylamino)-2-oxoethyl)amino)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 325

508 methyl (S)-7-methyl-3-(2-(methyl(tetrahydro-2H-pyran-4-yl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 326

494 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(4-cyclopropylpiperazin-1-yl)ethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 327

507 methyl (S)-3-(2-((S)-3-carbamoylpyrrolidin-1-yl)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 328

494 methyl (S)-3-(2-((S)-3-carbamoylpyrrolidin-1-yl)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 329

505 methyl (S)-7-methyl-3-(2-(((3-methylisoxazol-5-yl)methyl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 330

494 methyl (S)-3-(2-((2-cyanoethyl)amino)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 331

494 methyl (S)-3-(2-((isoxazol-5-ylmethyl)amino)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 332

466 methyl (S)-3-(2-(4-cyanopiperidin-1-yl)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 333

521 methyl (S)-3-(2-((R)-3-acetamidopyrrolidin-1-yl)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 334

521 methyl (S)-3-(2-((S)-3-acetamidopyrrolidin-1-yl)ethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Example 335: methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((S)-3-acetamidopyrrolidin-1-yl)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Step 1. Synthesis of methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((S)-3-acetamidopyrrolidin-1-yl)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

To a solution of(S)-2-(2-(2-(1H-pyrazol-1-yl)ethyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-3-yl)aceticacid (0.2 M 1,4-dioxane with 10% DIEA, 100 μL, 0.02 mmol), was added asolution of (S)-N-(pyrrolidin-3-yl)acetamide (0.2 M in 1,4-dioxane, 120μL, 0.024 mmol) and 2 a solution of DMC (0.2 M 1,2-DCE, 120 μL, 0.024mmol). The resulting mixture was put on a shaker at rt for 20 h. Themixture was then diluted with ethyl acetate (0.8 mL) and brine (0.45mL). The organic layer was separated and the aqueous layer was extractedwith ethyl acetate. The combined organic layers were dried down and theresidue was purified by HPLC: Water Autopurification MS-directed HPLCprep fraction collection with the following conditions Column, WatersXBridge OBD C18, 5 um, 19×50 mm; flow rate 20 ml/min; mobile phase,water with 0.1% ammonium hydroxide (A) and methanol with 0.1% ammoniumhydroxide (B) running the following gradient: 0 to 2 mins (15% B), 2 to6 mins (15-100% B); Detector ZQ Mass Detector in electrospray ionizationmode. This provided 3.4 mg of methyl(S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((S)-3-acetamidopyrrolidin-1-yl)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate(6.70 μmol, 34% yield) was obtained. MS (ESI, pos. ion) m/z: 508 (M+1).

The following examples in TABLE 16 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof Example 335.

TABLE 16 LRMS Example m/z Number Structure and Compound Name [M + H]⁺336

489 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxo-2-((pyrimidin-4-ylmethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 337

489 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxo-2-((pyrimidin-2-ylmethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 338

502 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxo-2-((2-(pyridin-2-yl)ethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 339

504 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(((2-hydroxypyridin-4-yl)methyl)amino)-2-oxoethyl)-7-methyl-3,7,8,9-tetratydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 340

478 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-((oxazol-2-ylmethyl)amino)-2-oxoethyl)-3,7,8,9-tetratydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 341

488 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxo-2-((pyridin-4-ylmethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 342

478 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-((oxazol-5-ylmethyl)amino)-2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 343

506 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(((4,5-dimethyl-4H-1,2,4-triazol-3-yl)methyl)amino)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 344

491 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(((1-methyl-1H-pyrazol-4-yl)methyl)amino)-2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 345

491 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(((1-methyl-1H-pyrazol-3-yl)methyl)amino)-2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 346

488 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxo-2-((pyridin-3-ylmethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 347

481 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxo-2-((((R)-tetrahydrofuran-2-yl)methyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 348

509 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)amino)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 349

455 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(((R)-1-hydroxypropan-2-yl)amino)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 350

455 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((2-hydroxyethyl)(methyl)amino)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 351

496 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((2-(dimethylamino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 352

481 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(4-hydroxypiperidin-1-yl)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 353

495 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(4-(hydroxymethyl)piperidin-1-yl)-2-oxoetlyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 354

482 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((2-(dimethylamino)-2-oxoethyl)amino)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 355

508 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxo-2-((2-oxo-2-(pyrrolidin-1-yl)ethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 356

495 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(methyl(tetrahydro-2H-pyran-4-yl)amino)-2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 357

495 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxo-2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 358

481 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-oxo-2-((tetrahydro-2H-pyran-4-yl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 359

481 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(methyl((S)-tetrahydrofuran-3-yl)amino)-2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 360

494 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((S)-3-carbamoylpyrrolidin-1-yl)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 361

483 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((2-hydroxy-2-methylpropyl)(methyl)amino)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 362

481 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(((1-hydroxycyclobutyl)methyl)amino)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 363

492 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(((3-methylisoxazol-5-yl)methyl)amino)-2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 364

481 methyl (S)-2-(2-(1H-pyiazol-1-yl)ethyl)-7-methyl-3-(2-(((3-methyloxetan-3-yl)methyl)amino)-2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 365

453 methyl (S)-2-(2-(1H-pyracol-1-yl)ethyl)-7-methyl-3-(2-(oxetan-3-ylamino)-2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]qninoline-6-carboxylate 366

436 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((cyanomethyl)amino)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydno-6H-imidazo[4,5-f]quinoline-6-carboxylate 367

478 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((isoxazol-5-ylmethyl)amino)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 368

478 methyl (S)-2-(2-(1H-pyiazol-1-yl)ethyl)-7-methyl-3-(2-oxo-2-((2-(2-oxoimidazolidin-1-yl)ethyl)amino)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 369

489 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-(4-cyanopiperidin-1-yl)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 370

508 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-3-(2-((R)-3-acetamidopyrrolidin-1-yl)-2-oxoethyl)-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 371

492 methyl (S)-2-(2-(1H-pyrazol-1-yl)ethyl)-7-methyl-3-(2-(((1-methyl-1H-1,2,4-triazol-5-yl)methyl)amino)-2-oxoethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 372

519 methyl (S)-7-methyl-3-(2-(((1-methyl-1H-1,2,4-triazol-5-yl)methyl)amino)-2-oxoethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 373

516 methyl (S)-7-methyl-3-(2-oxo-2-((pyrimidin-4-ylmethyl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 374

529 methyl (S)-7-methyl-3-(2-oxo-2-((2-(pyridin-2-yl)ethyl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 375

515 methyl (S)-7-methyl-3-(2-oxo-2-((pyridin-3-ylmethyl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 376

508 methyl (S)-7-methyl-3-(2-oxo-2-((((R)-tetrahydrofuran-2-yl)methyl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 377

536 methyl (S)-3-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)amino)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 378

482 mmethyl (S)-3-(2-(((R)-1-hydroxypropan-2-yl)amino)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 379

482 methyl (S)-3-(2-((2-hydroxyethyl)(methyl)amino)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 380

523 methyl (S)-3-(2-((2-(dimethylamino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 381

508 methyl (S)-3-(2-(4-hydroxypiperidin-1-yl)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 382

509 methyl (S)-3-(2-((2-(dimethylamino)-2-oxoethyl)amino)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 383

535 methyl (S)-7-methyl-3-(2-oxo-2-((2-oxo-2-(pyrrolidin-1-yl)ethyl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 384

522 methyl (S)-7-methyl-3-(2-(methyl(tetrahydro-2H-pyran-4-yl)amino)-2-oxoethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 385

522 methyl (S)-7-methyl-3-(2-oxo-2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 386

508 methyl (S)-7-methyl-3-(2-oxo-2-((tetrahydro-2H-pyran-4-yl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 387

508 methyl (S)-7-methyl-3-(2-(methyl((S)-tetrahydrofuran-3-yl)amino)-2-oxoethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 388

521 methyl (S)-3-(2-((S)-3-carbamoylpyrrolidin-1-yl)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 389

510 methyl (S)-3-(2-((2-hydroxy-2-methylpropyl)(methyl)amino)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 390

508 methyl (S)-3-(2-(((1-hydroxycyclobutyl)methyl)amino)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 391

519 methyl (S)-7-methyl-3-(2-(((3-methylisoxazol-5-yl)methyl)amino)-2-oxoethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 392

508 mmethyl (S)-7-methyl-3-(2-(((3-methyloxetan-3-yl)methyl)amino)-2-oxoethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 393

480 methyl (S)-7-methyl-3-(2-(oxetan-3-ylamino)-2-oxoethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 394

463 methyl (S)-3-(2-((cyanomethyl)amino)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 395

536 methyl (S)-7-methyl-3-(2-oxo-2-((2-(2-oxoimidazolidin-1-yl)ethyl)amino)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 396

517 methyl (S)-3-(2-(4-cyanopiperidin-1-yl)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 397

535 methyl (S)-3-(2-((R)-3-acetamidopyrrolidin-1-yl)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 398

535 methyl (S)-3-(2-((S)-3-acetamidopyrrolidin-1-yl)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 399

494 methyl (S)-3-(2-((S)-3-hydroxypyrrolidin-1-yl)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 400

507 methyl (S)-7-methyl-3-(2-oxo-2-(3-oxopiperazin-1-yl)ethyl)-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 401

514 methyl (S)-3-(2-(3,3-difluoropyrrolidin-1-yl)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 402

530 methyl (S)-3-(2-(5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate 403

490 methyl (S)-3-(2-((1H-pyrazol-5-yl)amino)-2-oxoethyl)-7-methyl-2-(2-(2-oxopyridin-1(2H)-yl)ethyl)-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate

Example 413 and 501:(1R,3R)-3-[(7S)-2-[(R)-(4-chlorophenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid; and(1R,3R)-3-[(7S)-2-[(S)-(4-chlorophenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid

Step 1. 6-fluoro-2-methyl-5-nitroquinoline

A solution of trifluoromethanesulfonic acid (82.0 mL, 0.923 mol) in HNO₃(19.6 mL, 0.437 mol) was stirred for 20 min at 0° C. This was followedby the addition of 6-fluoro-2-methylquinoline (50.0 g, 0.310 mol) indichloromethane (300 mL) at 0° C. The resulting mixture was stirred for15 hours at room temperature (25° C.). The reaction mixture was dilutedwith water (300 mL). The pH value of the solution was adjusted to 8 withsodium bicarbonate (saturated aqueous solution). The resulting solutionwas extracted with dichloromethane (3×300 mL). The combined organiclayers were dried over anhydrous sodium sulfate, filtered, andconcentrated under vacuum. The residue was purified by silica gelchromatography (eluting with 1:4 ethyl acetate/petroleum ether) toafford 6-fluoro-2-methyl-5-nitroquinoline as a light yellow solid (60.0g, 94%). LCMS (ES, m/z): 207 [M+H]⁺

Step 2. (2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline

A solution of (S)-(−)-MeO-BIPHEP (1.03 g, 1.77 mmol),chloro(1,5-cyclooctadiene)iridium(I) dimer (538 mg, 0.80 mmol) intoluene (100 mL) was stirred for 30 min at room temperature (25° C.)under an atmosphere of nitrogen. This was followed by the addition of 12(410 mg, 1.62 mmol), and 6-fluoro-2-methyl-5-nitroquinoline (33.0 g,0.160 mol) in toluene (100 mL). The resulting mixture was stirred for 20h at room temperature (25° C.) under hydrogen (50 atm). The resultingmixture was concentrated under vacuum and purified by silica gelchromatography (eluting with 1:1 ethyl acetate/petroleum ether) toafford the crude product (35.0 g). The crude product was dissolved inethyl acetate (230 mL), followed by the addition of D-Camphorsulfonicacid (36.9 g, 0.158 mol). The resulting solution was stirred for 1 h at60° C. and then cooled to room temperature. The solids were collected byfiltration, and rinsed with ethyl acetate (120 mL). The solids weredissolved in water (50 mL). The pH value of the solution was adjusted to8 with sodium bicarbonate (saturated aqueous solution). The resultingsolution was extracted with ethyl acetate (3×120 mL). The combinedorganic layers was dried over anhydrous sodium sulfate, filtered, andconcentrated under vacuum to afford(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline as a redsolid (25.5 g, 76%). LCMS (ES, m/z): 211 [M+H]⁺

Step 3. methyl(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of (2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline(25.3 g, 0.120 mol), pyridine (39.0 mL, 0.484 mol), and methylcarbonochloridate (18.7 mL, 0.242 mol) in dichloromethane (150 mL) wasstirred for 3 h at room temperature (25° C.). The reaction was washedwith 1N hydrogen chloride (aq., 2×70 mL). The combined organic layerswere dried over anhydrous sodium sulfate, filtered, and concentratedunder vacuum to afford methyl(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylateas a yellow solid (29.8 g, 92%). LCMS (ES, m/z): 269 [M+H]⁺

Step 4. methyl(2S)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of methyl(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate(29.6 g, 0.110 mol), pyridine (29.6 mL, 0.368 mol), potassium carbonate(30.5 g, 0.220 mol), and methyl (1R,3R)-3-aminocyclohexane-1-carboxylate(25.6 g, 162.84 mmol) in DMSO (270 mL) was stirred for 15 h at 90° C.and then cooled to room temperature. The reaction was quenched by theaddition of water (200 mL) and extracted with ethyl acetate (3×300 mL).The combined organic layers were dried over anhydrous sodium sulfate,filtered, and concentrated under vacuum. The resulting crude product waspurified by silica gel chromatography (eluting with 1:1 ethylacetate/petroleum ether) to afford methyl(2S)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylateas a red oil (32 g, 72%). LCMS (ES, m/z): 406 [M+H]⁺

Step 5. methyl(2S)-5-amino-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of methyl(2S)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate(31.0 g, 76.46 mmol), NH₄Cl (24.3 g, 454.28 mmol), and Fe (powder, 64.3g, 1.15 mol) in tetrahydrofuran (300 mL), ethanol (300 mL), water (100mL) was stirred for 1 h at 80° C. and then cooled to room temperature.The solids were filtered out by filtration. The resulting solution wasdiluted with water (300 mL) and extracted with ethyl acetate (3×400 mL).The combined organic layers were dried over anhydrous sodium sulfate,filtered, and concentrated under vacuum to afford methyl(2S)-5-((R)-2-hydroxy-2-phenylacetamido)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylateas a dark green solid (27.5 g, 92%). LCMS (ES, m/z): 376 [M+H]⁺

Step 6. methyl(2S)-5-[2-(4-chlorophenyl)-2-hydroxyacetamido]-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of 2-(4-chlorophenyl)-2-hydroxyacetic acid (112 mg, 0.60mmol), HATU (304 mg, 0.80 mmol), methyl(2S)-5-amino-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(150 mg, 0.40 mmol), and DIEA (155 mg, 1.20 mmol) inN,N-dimethylformamide (2 mL) was stirred for 15 h at room temperature(25° C.). The resulting solution was diluted with water (30 mL), andextracted with ethyl acetate (3×50 mL). The organic layers were combinedand washed with brine (2×25 mL). The combined organic layers were driedover anhydrous sodium sulfate, filtered, and concentrated under vacuum.The resulting crude product was purified by silica gel chromatography(eluting with 1:1 ethyl acetate/petroleum ether) to afford methyl(2S)-5-[2-(4-chlorophenyl)-2-hydroxyacetamido]-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylateas yellow oil (70.0 mg, 32%). LCMS (ES, m/z): 544 [M+H]⁺.

Step 7. methyl(7S)-2-[(4-chlorophenyl)(hydroxy)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

A solution of methyl(2S)-5-[2-(4-chlorophenyl)-2-hydroxyacetamido]-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(60.0 mg, 0.11 mmol) in AcOH (2 mL) was stirred for 15 h at 40° C. andthen cooled to room temperature. The reaction mixture was diluted withwater (10 mL). The pH value of the solution was adjusted to 8 withsodium bicarbonate (saturated aqueous solution). The resulting solutionwas extracted with ethyl acetate (3×15 mL). The organic layers werecombined and dried over anhydrous sodium sulfate, filtered, andconcentrated under vacuum. The resulting crude product was purified bysilica gel chromatography (eluting with 1:1 ethyl acetate/petroleumether) to afford methyl(7S)-2-[(4-chlorophenyl)(hydroxy)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateas yellow oil (46.0 mg, 79%). LCMS (ES, m/z): 526 [M+H]⁺.

Step 8.(1R,3R)-3-[(7S)-2-[(R)-(4-chlorophenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid; and(1R,3R)-3-[(7S)-2-[(S)-(4-chlorophenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid

A solution of methyl(7S)-2-[(4-chlorophenyl)(hydroxy)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(50.0 mg, 0.10 mmol), and LiOH (11.4 mg, 0.48 mmol) in tetrahydrofuran(1 mL) and water (1 mL) was stirred for 15 h at 25° C. The resultingmixture was concentrated under vacuum. The crude product was purified byPrep-HPLC (Column: XBridge Shield RP18 OBD Column, 5 um, 19×150 mm;Mobile Phase, A: water (containing 10 mmol/L NH₄HCO₃) and B: ACN (10% to37% over 12 min); Detector: UV 254 nm). The product fractions werelyophilized to afford(1R,3R)-3-[(7S)-2-[(R)-(4-chlorophenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid as a white solid (10.5 mg, 43%); and(1R,3R)-3-[(7S)-2-[(S)-(4-chlorophenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid as a white solid (7.0 mg, 29%). The absolute stereochemisties areunknown and therefore are left undefined in Table 17.

First eluting isomer (413): ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49 (d,J=9.0 Hz, 1H), 7.42-7.33 (m, 5H), 6.19 (s, 1H), 4.92-4.90 (m, 1H),4.82-4.72 (m, 1H), 3.79 (s, 3H), 3.34-3.20 (m, 1H), 3.02-2.94 (m, 1H),2.90-2.87 (m, 1H), 2.36-2.09 (m, 4H), 1.99-1.96 (m, 1H), 1.80-1.42 (m,5H), 1.16 (d, J=6.6 Hz, 3H). LCMS (ES, m/z): 512 [M+H]⁺.

Second eluting isomer (501): ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52-7.33(m, 6H), 6.22 (s, 1H), 4.84-4.73 (m, 2H), 3.78 (s, 3H), 3.27-3.16 (m,1H), 3.04-2.92 (m, 1H), 2.90-2.88 (m, 1H), 2.46-2.35 (m, 2H), 2.30-2.22(m, 1H), 2.15-2.02 (m, 2H), 1.82-1.71 (m, 1H), 1.63-1.55 (m, 2H),1.40-1.28 (m, 1H), 1.15 (d, J=6.6 Hz, 4H). LCMS (ES, m/z): 512 [M+H]⁺.

Examples 424 and 660:(1R,3R)-3-[(7S)-2-[(R)-(5-fluoro-2-methoxyphenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid (424);(1R,3R)-3-[(7S)-2-[(S)-(5-fluoro-2-methoxyphenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid (660) Synthesis of intermediate2-(5-fluoro-2-methoxyphenyl)-2-hydroxyacetic acid

Step 1. 2-(5-fluoro-2-methoxyphenyl)-2-[(trimethylsilyl)oxy]acetonitrile

A solution of ZnI₂ (1.6 mg, 0.01 mmol), 5-fluoro-2-methoxybenzaldehyde(1.54 g, 9.99 mmol) in trimethylsilanecarbonitrile (1.5 mL, 11.25 mmol)was stirred for 1 h at room temperature. The resulting mixture wasconcentrated under vacuum. The resulting crude product was purified bysilica gel chromatography (eluting with 1:1 ethyl acetate/petroleumether) to afford2-(5-fluoro-2-methoxyphenyl)-2-[(trimethylsilyl)oxy]acetonitrile as awhite solid (2.0 g, 79%).

Step 2. 2-(5-fluoro-2-methoxyphenyl)-2-hydroxyacetic acid

A solution of2-(5-fluoro-2-methoxyphenyl)-2-[(trimethylsilyl)oxy]acetonitrile (1.50g, 5.92 mmol) in hydrogen chloride (10 mL, 12M). The resulting solutionwas stirred for 1 h at 25° C., and then stirred for 2 h at 70° C. Thereaction mixture was cooled and concentrated under vacuum. The crudeproduct was purified by reverse phase chromatography (Column: C18;Mobile phase, A: water (containing 0.05% TFA) and B: ACN (5% to 20% over30 min); Detector, UV 254 nm) to afford2-(5-fluoro-2-methoxyphenyl)-2-hydroxyacetic acid as a white solid (1.10g, 93%).

Step 3. 6-fluoro-2-methyl-5-nitroquinoline

A solution of trifluoromethanesulfonic acid (82.0 mL, 0.923 mol) in HNO₃(19.6 mL, 0.437 mol) was stirred for 20 min at 0° C. This was followedby the addition of 6-fluoro-2-methylquinoline (50.0 g, 0.310 mol) indichloromethane (300 mL) at 0° C. The resulting mixture was stirred for15 h at room temperature (25° C.). The reaction mixture was diluted withwater (300 mL). The pH value of the solution was adjusted to 8 withsodium bicarbonate (saturated aqueous solution). The resulting solutionwas extracted with dichloromethane (3×300 mL). The combined organiclayers were dried over anhydrous sodium sulfate, filtered, andconcentrated under vacuum. The residue was purified by silica gelchromatography (eluting with 1:4 ethyl acetate/petroleum ether) toafford 6-fluoro-2-methyl-5-nitroquinoline as a light yellow solid (60.0g, 94%). LCMS (ES, m/z): 207 [M+H]⁺

Step 4. (2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline

A solution of (S)-(−)-MeO-BIPHEP (1.03 g, 1.77 mmol),chloro(1,5-cyclooctadiene)iridium(I) dimer (538 mg, 0.80 mmol) intoluene (100 mL) was stirred for 30 min at room temperature (25° C.)under an atmosphere of nitrogen. This was followed by the addition of I₂(410 mg, 1.62 mmol), 6-fluoro-2-methyl-5-nitroquinoline (33.0 g, 0.160mol) in toluene (100 mL). The resulting mixture was stirred for 20 h atroom temperature (25° C.) under hydrogen (50 atm). The resulting mixturewas concentrated under vacuum and purified by silica gel chromatography(eluting with 1:1 ethyl acetate/petroleum ether) to afford the crudeproduct (35.0 g). The crude product was dissolved in ethyl acetate (230mL), followed by the addition of D-Camphorsulfonic acid (36.9 g, 0.158mol). The resulting solution was stirred for 1 h at 60° C. and thencooled to room temperature. The solids were collected by filtration, andrinsed with ethyl acetate (120 mL). The solids were dissolved in water(50 mL). The pH value of the solution was adjusted to 8 with sodiumbicarbonate (saturated aqueous solution). The resulting solution wasextracted with ethyl acetate (3×120 mL). The combined organic layers wasdried over anhydrous sodium sulfate, filtered, and concentrated undervacuum to afford(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline as a redsolid (25.5 g, 76%). LCMS (ES, m/z): 211 [M+H]⁺

Step 5. methyl(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of (2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline(25.3 g, 0.120 mol), pyridine (39.0 mL, 0.484 mol), methylcarbonochloridate (18.7 mL, 0.242 mol) in dichloromethane (150 mL) wasstirred for 3 h at room temperature (25° C.). The reaction was washedwith 1M hydrochorlic acid (2×70 mL). The combined organic layers wasdried over anhydrous sodium sulfate, filtered, and concentrated undervacuum to afford methyl(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylateas a yellow solid (29.8 g, 92%). LCMS (ES, m/z): 269 [M+H]⁺

Step 6. methyl(2S)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of methyl(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate(29.6 g, 0.110 mol), pyridine (29.6 mL, 0.368 mol), potassium carbonate(30.5 g, 0.220 mol), methyl (1R,3R)-3-aminocyclohexane-1-carboxylate(25.6 g, 162.84 mmol) in DMSO (270 mL) was stirred for 15 h at 90° C.and then cooled to room temperature. The reaction was quenched by theaddition of water (200 mL) and extracted with ethyl acetate (3×300 mL).The combined organic layers was dried over anhydrous sodium sulfate,filtered, and concentrated under vacuum.

The resulting crude product was purified by silica gel chromatography(eluting with 1:1 ethyl acetate/petroleum ether) to afford methyl(2S)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylateas a red oil (32 g, 72%). LCMS (ES, m/z): 406 [M+H]⁺

Step 7. methyl(2S)-5-amino-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of methyl(2S)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate(31.0 g, 76.46 mmol), NH₄Cl (24.3 g, 454.28 mmol), Fe (64.3 g, 1.15 mol)in tetrahydrofuran (300 mL), ethanol (300 mL), water (100 mL) wasstirred for 1 h at 80° C. and then cooled to room temperature. Thesolids were filtered out by filtration. The resulting solution wasdiluted with water (300 mL) and extracted with ethyl acetate (3×400 mL).The combined organic layers was dried over anhydrous sodium sulfate,filtered, and concentrated under vacuum to afford methyl(2S)-5-amino-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylateas a dark green solid (27.5 g, 96%). LCMS (ES, m/z): 376 [M+H]⁺

Step 8. methyl(2S)-5-[2-(5-fluoro-2-methoxyphenyl)-2-hydroxyacetamido]-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of 2-(5-fluoro-2-methoxyphenyl)-2-hydroxyacetic acid (240 mg,1.20 mmol), HATU (228 mg, 0.60 mmol), methyl(2S)-5-amino-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(150 mg, 0.40 mmol), and DIEA (0.19 mL, 1.20 mmol) inN,N-dimethylformamide (10 mL) was stirred for 1 h at 25° C. Theresulting solution was diluted with H₂O (10 mL). The resulting solutionwas extracted with ethyl acetate (3×15 mL) and the organic layerscombined. The resulting mixture was washed with brine (2×20 mL). Themixture was dried over anhydrous sodium sulfate and concentrated undervacuum. The resulting crude product was purified by silica gelchromatography (eluting with 3:2 ethyl acetate/petroleum ether) toafford methyl(2S)-5-[2-(5-fluoro-2-methoxyphenyl)-2-hydroxyacetamido]-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylateas a yellow solid (180 mg, 81%). LCMS (ES, m z): 558 [M+H]⁺

Step 9. methyl(7S)-2-[(5-fluoro-2-methoxyphenyl)(hydroxy)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

A solution of methyl(2S)-5-[2-(5-fluoro-2-methoxyphenyl)-2-hydroxyacetamido]-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(180 mg, 0.32 mmol) in AcOH (8 mL) was stirred for overnight at 60° C.The reaction mixture was cooled and concentrated under vacuum. Theresulting crude product was purified by silica gel chromatography(eluting with 1:1 ethyl acetate/petroleum ether) to afford methyl(7S)-2-[(5-fluoro-2-methoxyphenyl)(hydroxy)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateas a yellow solid (120 mg, 69%). LCMS (ES, m/z): 540 [M+H]⁺

Step 10.(1R,3R)-3-[(7S)-2-[(R)-(5-fluoro-2-methoxyphenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid;(1R,3R)-3-[(7S)-2-[(S)-(5-fluoro-2-methoxyphenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid

A solution of methyl(7S)-2-[(5-fluoro-2-methoxyphenyl)(hydroxy)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(120 mg, 0.22 mmol), and LiOH (16 mg, 0.67 mmol) in tetrahydrofuran (2.0mL), methanol (2.0 mL) and water (2.0 mL) was stirred overnight at 25°C. The resulting mixture was concentrated under vacuum. The crudeproduct was purified by Prep-HPLC (Column, XBridge Prep C18 OBD Column,19×150 mm, 5 um; Mobile phase, A: water (containing 10 mmol/L NH₄HCO₃)and B: ACN (15.0% to 29.0% over 14 min); Detector, UV 220/254 nm). Theproduct was separated by Chiral-Prep-HPLC (Column, CHIRALPAK IE, 2×25cm, 5 um; Mobile phase, A: Hex (containing 0.1% FA) and B: ethanol (hold50.0% ethanol over 12 min); Detector, UV 220/254 nm). The productfractions were concentrated to afford(1R,3R)-3-[(7S)-2-[(R)-(5-fluoro-2-methoxyphenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid as a white solid (23.6 mg, 20%); and(1R,3R)-3-[(7S)-2-[(S)-(5-fluoro-2-methoxyphenyl)(hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid as a white solid (23.8 mg, 2%). Enantiomeric excess was determinedvia HPLC: Column: CHIRALPAK IE-3, Column size:0.46×5 cm; 3 μm; Mobilephase: Hex (0.1% FA): EtOH=50:50, Flow: 1.0 ml/min. For clarity, theabsolute chemistry of each of compounds 424 and 660 was not included intable 17 however is shown in the scheme above.

First eluting isomer (424): ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56-7.47(m, 1H), 7.47-7.31 (m, 1H), 7.21-7.09 (m, 1H), 7.09-6.89 (m, 2H), 6.53(s, 1H), 4.81-4.61 (m, 2H), 3.85 (s, 3H), 3.78 (s, 3H), 3.31-3.18 (m,1H), 3.06-2.82 (m, 2H), 2.57-2.41 (m, 1H), 2.41-2.31 (m, 1H), 2.31-2.09(m, 3H), 1.83-1.58 (m, 3H), 1.49-1.21 (m, 2H), 1.16 (d, J=6.8 Hz, 3H).LCMS (ES, m/z): 526 [M+H]⁺.

Second eluting isomer (660): ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.69-7.44(m, 2H), 7.44-7.29 (m, 1H), 7.12-6.99 (m, 1H), 6.98-6.82 (m, 1H), 6.37(s, 1H), 5.03-4.91 (m, 1H), 4.81-4.69 (m, 1H), 3.78 (s, 3H), 3.61 (s,3H), 3.22-3.04 (m, 1H), 3.02-2.87 (m, 2H), 2.54-2.41 (m, 1H), 2.41-2.27(m, 1H), 2.27-2.08 (m, 3H), 1.82-1.58 (m, 3H), 1.58-1.41 (m, 2H), 1.14(d, J=6.4 Hz, 3H). LCMS (ES, m/z): 526 [M+H]⁺.

Examples 452 and 515:(1R,3R)-3-[(7S)-2-[(S)-[2-(difluoromethoxy)-5-fluorophenyl](hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid (515),(1R,3R)-3-[(7S)-2-[(R)-[2-(difluoromethoxy)-5-fluorophenyl](hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid (452) Synthesis of intermediate2-(2-(difluoromethoxy)-5-fluorophenyl)-2-hydroxyacetic acid

Step 1. 2-(difluoromethoxy)-5-fluorobenzaldehyde

A solution of 5-fluoro-2-hydroxybenzaldehyde (2.0 g, 14.3 mmol), diethyl(bromodifluoromethyl)phosphonate (5.69 g, 21.3 mmol), potassiumhydroxide (16.0 g, 285 mmol) in MeCN (100 mL) and water (50 mL) wasstirred for 1 h at −30° C. The reaction mixture was diluted with water(20 mL). The resulting solution was extracted with ethyl acetate (3×100mL) and the organic layers combined and dried over anhydrous sodiumsulfate. The solids were filtered out. The resulting mixture wasconcentrated under vacuum. The resulting crude product was purified bysilica gel chromatography (eluting with 1:1 ethyl acetate/petroleumether) to afford 2-(difluoromethoxy)-5-fluorobenzaldehyde as a yellowsolid (1.46 g, 54%). LCMS (ES, m/z): 191 [M+H]⁺

Step 2.2-[2-(difluoromethoxy)-5-fluorophenyl]-2-[(trimethylsilyl)oxy]acetonitrile

A solution of 2-(difluoromethoxy)-5-fluorobenzaldehyde (1.46 g, 7.68mmol), TMSCN (760 mg, 7.66 mmol), ZnI₂ (50 mg, 0.16 mmol) indichloromethane (3 mL) was stirred for 2 h at room temperature (25° C.).The resulting mixture was concentrated under vacuum. The resulting crudeproduct was purified by silica gel chromatography (eluting with 1:1ethyl acetate/petroleum ether) to afford2-[2-(difluoromethoxy)-5-fluorophenyl]-2-[(trimethylsilyl)oxy]acetonitrileas a yellow solid (800 mg, 36%). LCMS (ES, m/z):290 [M+H]⁺

Step 3. 2-[2-(difluoromethoxy)-5-fluorophenyl]-2-hydroxyacetic acid

A solution of2-[2-(difluoromethoxy)-5-fluorophenyl]-2-[(trimethylsilyl)oxy]acetonitrile(800 mg, 2.77 mmol), 1,4-dioxane (2.0 mL), hydrogen chloride (1.0 mL,12M) in water (2 mL) was stirred for 12 h at 70° C. and then cooled toroom temperature. The resulting solution was concentrated under vacuum.The crude product was purified by reverse phase column chromatography(water (containing 0.05% TFA)/MeCN) to afford2-[2-(difluoromethoxy)-5-fluorophenyl]-2-hydroxyacetic acid (400 mg,61%). LCMS (ES, m/z): 237 [M+H]⁺

Step 4. methyl(2S)-5-[2-[2-(difluoromethoxy)-5-fluorophenyl]-2-hydroxyacetamido]-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of methyl(2S)-5-amino-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(prepared as in the scheme above for Example 424 and 660) (200 mg, 0.53mmol), 2-[2-(difluoromethoxy)-5-fluorophenyl]-2-hydroxyacetic acid (220mg, 0.93 mmol), DMTMM (350 mg, 1.26 mmol) in dichloromethane (5 mL) wasstirred for 1 h room temperature (25° C.). The resulting solution wasconcentrated under vacuum. The resulting crude product was purified bysilica gel chromatography (eluting with 1:1 ethyl acetate/petroleumether) to afford methyl(2S)-5-[2-[2-(difluoromethoxy)-5-fluorophenyl]-2-hydroxyacetamido]-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylateas a yellow solid (70.0 mg, 22%). LCMS (ES, m/z): 594 [M+H]⁺

Step 5. methyl(7S)-2-[[2-(difluoromethoxy)-5-fluorophenyl](hydroxy)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

A solution of methyl(2S)-5-[2-[2-(difluoromethoxy)-5-fluorophenyl]-2-hydroxyacetamido]-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(70.0 mg, 0.12 mmol) in glacial acetic acid (2.0 mL) was stirred forovernight at 40° C. and then cooled to room temperature. The resultingsolution was concentrated under vacuum. The resulting crude product waspurified by silica gel chromatography (eluting with 1:2 ethylacetate/petroleum ether) to afford methyl(7S)-2-[[2-(difluoromethoxy)-5-fluorophenyl](hydroxy)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylateas a yellow solid (50.0 mg, 74%). LCMS (ES, m/z): 576 [M+H]⁺

Step 6.(1R,3R)-3-[(7S)-2-[(S)-[2-(difluoromethoxy)-5-fluorophenyl](hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid;(1R,3R)-3-[(7S)-2-[(R)-[2-(difluoromethoxy)-5-fluorophenyl](hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid

A solution of methyl(7S)-2-[[2-(difluoromethoxy)-5-fluorophenyl](hydroxy)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(50.0 mg, 0.09 mmol), LiOH (10.0 mg, 0.42 mmol) in tetrahydrofuran (2.0mL) and water (2.0 mL) was stirred for overnight at room temperature(25° C.). The resulting mixture was concentrated under vacuum. The crudeproduct was purified by Prep-HPLC (Column, XBridge Shield RP18 OBDColumn, 30×150 mm, 5 um; Mobile phase, A: water (containing 10 mmol/LNH₄HCO₃) and B: ACN (25.0% to 35.0% over 8 min); Detector, UV 254/220nm). The product fractions were concentrated to afford(1R,3R)-3-[(7S)-2-[(S)-[2-(difluoromethoxy)-5-fluorophenyl](hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid as a white solid (4.50 mg, 9%), and(1R,3R)-3-[(7S)-2-[(R)-[2-(difluoromethoxy)-5-fluorophenyl](hydroxy)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid as a white solid (4.30 mg, 9%). Enantiomeric excess was determinedvia HPLC: Column: CHIRALPAK IE-3, Column size:0.46×5 cm; 3 μm;Co-Solvent: IPA (20 mM NH₃) Gradient (B %): 10% to 50% in 4.0 min, hold2.0 min at 50%. For clarity, the absolute chemistry of each of compounds452 and 515 was not included in table 17 however is shown in the schemeabove.

First eluting isomer (515): ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.63-7.61(m, 1H), 7.53 (d, J=8.8 Hz, 1H), 7.41 (d, J=9.2 Hz, 1H) 7.20-7.13 (m,2H), 6.67-6.30 (m, 2H), 4.98-4.95 (m, 1H), 4.76-4.71 (m, 1H), 3.78 (s,3H), 3.15-2.86 (m, 3H), 2.46-2.20 (m, 5H), 1.81-1.53 (m, 5H), 1.13 (d,J=6.8 Hz, 3H). LCMS (ES, m/z): 562 [M+H]⁺.

Second eluting isomer (452): ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55-7.53(m, 1H), 7.47-7.42 (m, 2H), 7.40-7.12 (m, 2H), 6.85-6.44 (m, 2H),4.94-4.91 (m, 1H), 4.76-4.71 (m, 1H), 3.78 (s, 3H), 3.22-2.84 (m, 3H),2.46-2.23 (m, 5H), 1.84-1.61 (m, 5H), 1.14 (d, J=6.4 Hz, 3H). LCMS (ES,m/z): 562 [M+H]⁺; >99.99% ee.

Example 462:(1R,3R)-3-[(7S)-2-[(R)-hydroxy(phenyl)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid

Step 1. 6-fluoro-2-methyl-5-nitroquinoline

A solution of trifluoromethanesulfonic acid (82.0 mL, 0.923 mol) in HNO₃(19.6 mL, 0.437 mol) was stirred for 20 min at 0° C. This was followedby the addition of 6-fluoro-2-methylquinoline (50.0 g, 0.310 mol) indichloromethane (300 mL) at 0° C. The resulting mixture was stirred for15 h at room temperature (25° C.). The reaction mixture was diluted withwater (300 mL). The pH value of the solution was adjusted to 8 withsodium bicarbonate (saturated aqueous solution). The resulting solutionwas extracted with dichloromethane (3×300 mL). The combined organiclayers were dried over anhydrous sodium sulfate, filtered, andconcentrated under vacuum. The residue was purified by silica gelchromatography (eluting with 1:4 ethyl acetate/petroleum ether) toafford 6-fluoro-2-methyl-5-nitroquinoline as a light yellow solid (60.0g, 94%). LCMS (ES, m/z): 207 [M+H]⁺

Step 2. (2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline

A solution of (S)-(−)-MeO-BIPHEP (1.03 g, 1.77 mmol),chloro(1,5-cyclooctadiene)iridium(I) dimer (538 mg, 0.80 mmol) intoluene (100 mL) was stirred for 30 min at room temperature (25° C.)under an atmosphere of nitrogen. This was followed by the addition of I₂(410 mg, 1.62 mmol), 6-fluoro-2-methyl-5-nitroquinoline (33.0 g, 0.160mol) in toluene (100 mL). The resulting mixture was stirred for 20 h atroom temperature (25° C.) under hydrogen (50 atm). The resulting mixturewas concentrated under vacuum and purified by silica gel chromatography(eluting with 1:1 ethyl acetate/petroleum ether) to afford the crudeproduct (35.0 g). The crude product was dissolved in ethyl acetate (230mL), followed by the addition of D-Camphorsulfonic acid (36.9 g, 0.158mol). The resulting solution was stirred for 1 h at 60° C. and thencooled to room temperature. The solids were collected by filtration, andrinsed with ethyl acetate (120 mL). The solids were dissolved in water(50 mL). The pH value of the solution was adjusted to 8 with sodiumbicarbonate (saturated aqueous solution). The resulting solution wasextracted with ethyl acetate (3×120 mL). The combined organic layers wasdried over anhydrous sodium sulfate, filtered, and concentrated undervacuum to afford(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline as a redsolid (25.5 g, 76%). LCMS (ES, m/z): 211 [M+H]⁺

Step 3. methyl(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of (2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline(25.3 g, 0.120 mol), pyridine (39.0 mL, 0.484 mol), methylcarbonochloridate (18.7 mL, 0.242 mol) in dichloromethane (150 mL) wasstirred for 3 h at room temperature (25° C.). The reaction was washedwith 1M hydrogen chloride (2×70 mL). The combined organic layers wasdried over anhydrous sodium sulfate, filtered, and concentrated undervacuum to afford methyl(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylateas a yellow solid (29.8 g, 92%). LCMS (ES, m/z): 269 [M+H]⁺

Step 4. methyl(2S)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of methyl(2S)-6-fluoro-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate(29.6 g, 0.110 mol), pyridine (29.6 mL, 0.368 mol), potassium carbonate(30.5 g, 0.220 mol), methyl (1R,3R)-3-aminocyclohexane-1-carboxylate(25.6 g, 162.84 mmol) in DMSO (270 mL) was stirred for 15 h at 90° C.and then cooled to room temperature. The reaction was quenched by theaddition of water (200 mL) and extracted with ethyl acetate (3×300 mL).The combined organic layers was dried over anhydrous sodium sulfate,filtered, and concentrated under vacuum. The resulting crude product waspurified by silica gel chromatography (eluting with 1:1 ethylacetate/petroleum ether) to afford methyl(2S)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylateas a red oil (32 g, 72%). LCMS (ES, m/z): 406 [M+H]⁺

Step 5. methyl(2S)-5-amino-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of(2S)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-5-nitro-1,2,3,4-tetrahydroquinoline-1-carboxylate(31.0 g, 76.46 mmol), NH₄Cl (24.3 g, 454.28 mmol), Fe (64.3 g, 1.15 mol)in tetrahydrofuran (300 mL), ethanol (300 mL), water (100 mL) wasstirred for 1 h at 80° C. and then cooled to room temperature. Thesolids were filtered out by filtration. The resulting solution wasdiluted with water (300 mL) and extracted with ethyl acetate (3×400 mL).The combined organic layers was dried over anhydrous sodium sulfate,filtered, and concentrated under vacuum to afford methyl(2S)-5-amino-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylateas a dark green solid (27.5 g, 92%). LCMS (ES, m/z): 376 [M+H]⁺

Step 6. methyl(2S)-5-((R)-2-hydroxy-2-phenylacetamido)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

A solution of (R)-2-hydroxy-2-phenylacetic acid (972 mg, 6.39 mmol),HATU (1.20 g, 3.16 mmol), methyl(2S)-5-amino-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(800 mg, 2.13 mmol), DIEA (1.08 mL, 6.20 mmol) in N,N-dimethylformamide(10 mL) was stirred for 5 h at room temperature (25° C.). The resultingsolution was diluted with water (30 mL), and extracted with ethylacetate (3×50 mL). The organic layers were combined and washed withbrine (2×25 mL). The combined organic layers was dried over anhydroussodium sulfate, filtered, and concentrated under vacuum. The resultingcrude product was purified by silica gel chromatography (eluting with1:1 ethyl acetate/petroleum ether) to afford methyl(2S)-5-((R)-2-hydroxy-2-phenylacetamido)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylateas a colorless oil (600 mg, 55%). LCMS (ES, m/z): 510 [M+H]⁺

Step 7. methyl(7S)-2-[(R)-hydroxy(phenyl)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate

A solution of methyl(2S)-5-((R)-2-hydroxy-2-phenylacetamido)-6-[[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]amino]-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate(600 mg, 1.18 mmol) in glacial acetic acid (5 mL, 98%) was stirred forovernight at 40° C. and then cooled to room temperature. The reactionmixture was diluted with water (10 mL). The pH value of the solution wasadjusted to 8 with sodium bicarbonate (saturated aqueous solution). Theresulting solution was extracted with ethyl acetate (3×15 mL). Theorganic layers were combined and dried over anhydrous sodium sulfate,filtered, and concentrated under vacuum. The resulting crude product waspurified by silica gel chromatography (eluting with 1:1 ethylacetate/petroleum ether) to afford methyl(7S)-2-[(R)-hydroxy(phenyl)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(400 mg, 69%) as a colorless oil. LCMS (ES, m/z): 492 [M+H]⁺

Step 8.(1R,3R)-3-[(7S)-2-[(R)-hydroxy(phenyl)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid

A solution of methyl(7S)-2-[(R)-hydroxy(phenyl)methyl]-3-[(1R,3R)-3-(methoxycarbonyl)cyclohexyl]-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinoline-6-carboxylate(400 mg, 0.81 mmol), LiOH (100 mg, 4.17 mmol) in tetrahydrofuran (5 mL)and water (2 mL) was stirred for overnight at room temperature (25° C.).The resulting mixture was concentrated under vacuum. The crude productwas purified by Prep-HPLC (Column: XBridge Shield RP18 OBD Column, 5 um,19×150 mm; Mobile Phase, A: water (containing 10 mmol/L NH₄HCO₃) and B:ACN (3% to 30% over 21 min); Detector: UV 254 nm). The product fractionswere lyophilized to afford(1R,3R)-3-[(7S)-2-[(R)-hydroxy(phenyl)methyl]-6-(methoxycarbonyl)-7-methyl-3H,6H,7H,8H,9H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylicacid as a white solid (83.7 mg, 22%). Enantiomeric excess was determinedvia HPLC: Column: CHIRALPAK IE-3, Column size:0.46×5 cm; 3 μm; Mobilephase: Hex (0.1% FA): EtOH=85:15, Flow:1.0 ml/min. For clarity, theabsolute chemistry was not included in table 17 however is shown hereinstead. ¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47-7.28 (m, 7H), 6.12 (s,1H), 4.84-4.74 (m, 2H), 3.79 (s, 3H), 3.33-3.25 (m, 1H), 3.03-2.96 (m,1H), 2.86-2.82 (m, 1H), 2.38-2.25 (m, 2H), 2.25-2.07 (m, 3H), 1.79-1.72(m, 1H), 1.64-1.57 (m, 2H), 1.40-1.29 (m, 2H), 1.16 (d, J=6.8 Hz, 3H).LCMS (ES, m/z): 478 [M+H]⁺; 99.13% ee.

The following examples in TABLE 17 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof previous Examples.

TABLE 17 LRMS Example m/z Number Structure and Compound Name [M + H] ¹HNMR 404¹

506 ¹HNMR (CD₃OD, 300 MHz) δ (ppm): 7.31-7.05 (m, 7H), 4.70-4.61 (m,1H), 4.18-3.89 (m, 2H), 3.67 (s, 3H), 3.66-3.51 (m, 1H), 3.38-3.31 (m,1H), 3.28 (s, 3H), 3.15-2.98 (m, 1H), 2.88-2.76 (m, 1H), 2.24-1.95 (m,3H), 1.92-1.80 (m, 3H), 1.75-1.54 (m, 2H), 1.28-1.11 (m, 2H), 1.01 (d, J= 6.6 Hz, 3H), 0.86-0.81 (m, 1H). 405²

526 ¹HNMR (CD₃OD, 400 MHz) δ (ppm): 7.41 (d, J = 9.2 Hz, 1H), 7.29 (d, J= 8.8 Hz, 1H), 7.06-7.01 (m, 2H), 6.84-6.86 (m, 1H), 4.73-4.64 (m, 2H),3.76 (s, 3H), 3.70-3.64 (m, 1H), 3.31-3.14 (m, 2H), 3.08-3.04 (m, 1H),2.95-2.80 (m, 2H), 2.28-2.19 (m, 5H), 1.72-1.47 (m, 7H), 1.12 (d, J =6.8 Hz, 3H), 1.09-0.92 (m, 1H). 406²

490 ¹HNMR (CD₃OD, 400 MHz) δ (ppm): 7.37 (d, J = 9.2 Hz, 1H), 7.27 (d, J= 8.8 Hz, 1H), 7.17-7.10 (m, 3H), 7.03 (d, J = 6.8 Hz, 2H), 4.88-4.72(m, 1H), 4.48-4.35 (m, 1H), 3.77 (s, 3H), 3.70-3.61 (m, 1H), 3.33-3.21(m, 1H), 3.18-3.01 (m, 2H), 2.98-2.86 (m, 2H), 2.31-1.95 (m, 5H),1.75-1.53 (m, 6H), 1.35-1.28 (m, 1H), 1.12 (d, J = 6.4 Hz, 3H),0.90-0.81 (m, 1H). 407¹

510 ¹HNMR (CD₃OD, 300 MHz) δ (ppm): 7.60 (d, J = 9.0 Hz, 1H), 7.49 (d, J= 9.0 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 7.13 (d, J = 7.2 Hz, 1H), 7.05(d, J = 9.0 Hz, 1H), 4.88-4.77 (m, 1H), 4.65-4.60 (m, 1H), 4.33-4.28 (m,1H), 3.96-3.80 (m, 3H), 3.77 (s, 3H), 3.75-3.72 (m, 1H), 3.58-3.34 (m,2H), 3.24-3.09 (m, 2H), 2.51-2.20 (m, 5H), 1.83-1.74 (m, 3H), 1.44-1.35(m, 1H), 1.14 (d, J = 6.6 Hz, 3H). 408²

546 ¹HNMR (CD₃OD, 400 MHz) δ (ppm): 7.47 (d, J = 8.8 Hz, 1H), 7.40 (d, J= 9.2 Hz, 1H), 7.26 (t, J = 8.0 Hz, 1H), 7.18 (d, J6.4 Hz, 1H), 7.08 (d,J = 8.4 Hz, 1H), 6.99-6.87 (t, 1H), 4.87-4.74 (m, 1H), 4.41 (s, 2H),4.24-4.20 (m, 1H), 3.77 (s, 3H), 3.20-3.16 (m, 1H), 2.99-2.93 (m, 1H),2.42-2.20 (m, 4H), 2.08-2.05 (m, 2H), 1.77-1.72 (m, 1H), 1.58-1.46 (m,4H), 1.14 (d, J = 6.8 Hz, 3H). 409²

504 ¹HNMR (CD₃OD, 400 MHz) δ (ppm): 7.49 (d, J = 9.2 Hz, 1H), 7.39 (d, J= 8.8 Hz, 1H), 7.24-7.19 (m, 4H), 6.90-6.82 (m, 1H), 5.48-5.40 (m, 1H),4.74-4.69 (m, 1H), 3.77 (s, 3H), 3.28-2.92 (m, 3H), 2.58-2.29 (m, 5H),1.84-1.59 (m, 6H), 1.43-1.30 (m, 3H), 1.13 (d, J = 6.4 Hz, 3H). 410²

527 ¹HNMR (CD₃OD, 400 MHz) δ (ppm): 7.68 (d, J = 8.0 Hz, 1H), 7.53 (d, J= 8.8 Hz, 1H), 7.42 (d, J = 9.2 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H),4.91-4.76 (m, 3H), 4.52-4.45 (m, 1H), 3.92 (s, 3H), 3.79 (s, 3H),3.24-3.16 (m, 1H), 2.98-2.92 (m, 2H), 2.41-2.19 (m, 5H), 1.78-1.61 (m,3H), 1.48-1.29 (m, 2H), 1.15 (d, J = 6.8 Hz, 3H), 411²

492 ¹HNMR (CD₃OD, 400 MHz) δ (ppm): 7.50 (d, J = 9.2 Hz, 1H), 7.41 (d, J= 9.2 Hz, 1H), 7.22-7.18 (m, 2H), 6.99-6.88 (m, 3H), 5.87-5.83 (m, 1H),5.33-5.28 (m, 1H), 4.79-4.75 (m, 1H), 3.78 (s, 3H), 3.20-2.94 (m, 3H),2.51-2.09 (m, 5H), 1.94 (d, J = 6.8 Hz, 3H), 1.76-1.58 (m, 4H),1.37-1.29 (m, 1H), 1.14 (d, J = 6.4 Hz, 3H). 412²

538 ¹HNMR (CD₃OD, 400 MHz) δ (ppm): 7.44 (d, J = 8.8 Hz, 1H), 7.38 (d, J= 9.2 Hz, 1H), 7.07-6.89 (m, 3H), 4.78-4.74 (m, 1H), 4.56.4.53 (m, 1H),4.32 (s, 2H), 4.25-4.21 (m, 1H), 3.77 (s, 3H), 3.31-3.16 (m, 1H),2.99-2.93 (m, 1H), 2.41-2.17 (m, 4H), 2.07-2.03 (m, 2H), 1.77-1.73 (m,1H), 1.55-1.43 (m, 4H), 1.28 (d, J = 6.0 Hz, 6H), 1.14 (d, J = 6.8 Hz,3H). 413 

512 ¹HNMR (CD₃OD, 400 MHz) δ (ppm): 7.49 (d, J = 9.0 Hz, 1H), 7.42-7.33(m, 5H), 6.19 (s, 1H), 4.92-4.90 (m, 1H), 4.82-4.72 (m, 1H), 3.79 (s,3H), 3.34-3.20 (m, 1H), 3.02-2.94 (m, 1H), 2.90-2.87 (m, 1H), 2.36-2.09(m, 4H), 1.99-1.96 (m, 1H), 1.80-1.42 (m, 5H), 1.16 (d, J = 6.6 Hz, 3H).¹Prepared using standard chemical manipulations and procedures similarto those used for the preparation of Example 139. ²Prepared usingstandard chemical manipulations and procedures similar to those used forthe preparation of Example 16.

The following examples in TABLE 18 were prepared using standard chemicalmanipulations and procedures similar to those used for the preparationof previous Examples.

TABLE 18 Example Number Structure and Compound Name ¹H NMR, LCMS 414

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.53-7.38 (m, 2H), 7.22-7.19 (m, 1H),7.09-7.04 (m, 2H), 6.16 (s, 1H), 4.86-4.70 (m, 2H), 3.79 (s, 3H),3.30-3.21 (m, 1H), 3.01-2.92 (m, 1H), 2.88-2.84 (m, 1H), 2.43-2.23 (m,5H), 2.15-2.04 (m, 2H), 2.01-1.97 (m, 1H), 1.81-1.60 (m, 3H), 1.56-1.38(m, 2H), 1.16 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 510 [M + H]⁺. 415

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.61-7.52 (m, 2H), 7.33-7.18 (m, 2H),7.11-7.09 (m, 1H), 6.26 (s, 1H), 5.02-4.99 (m, 1H), 4.80-4.79 (m, 1H),3.80 (s, 3H), 3.21-3.16 (m, 1H), 3.08-2.90 (m, 2H), 2.49-2.41 (m, 1H),2.35-2.22 (m, 5H), 2.14-2.03 (m, 2H), 1.81-1.79 (m, 1H), 1.63-1.58 (m,2H), 1.45-1.30 (m, 1H), 1.21-1.18 (m, 1H), 1.16 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 510 [M + H]⁺. 416

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.71-7.54 (m, 2H), 7.54-7.42 (m, 1H),7.42-7.29 (m, 1H), 7.19-6.97 (m, 1H), 6.20 (s, 1H), 4.99-4.89 (m, 1H),4.82-4.74 (m, 1H), 3.98 (s, 3H), 3.89 (s, 3H), 3.29-3.19 (m, 1H),3.11-2.93 (m, 2H), 2.48-2.22 (m, 2H), 2.22-2.08 (m, 3H), 1.91-1.69 (m,3H), 1.38-1.24 (m, 2H), 1.18 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 542[M + H]⁺ 417

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51-7.42 (m, 2H), 6.94 (s, 1H),6.79-6.72 (m, 1H), 6.55-6.62 (m, 1H), 6.19 (s, 1H), 5.03-4.90 (m, 1H),4.84-4.70 (m, 1H), 3.82 (s, 3H), 3.81 (s, 3H), 3.28-3.10 (m, 1H),3.05-2.95 (m, 2H), 2.52-2.43 (m, 2H), 2.38-2.27 (m, 1H), 2.17-1.96 (m,2H), 1.81-1.66 (m, 1H), 1.64-1.58 (m, 2H), 1.43-1.30 (m, 1H), 1.15 (d, J= 6.8 Hz, 3H), 1.02-0.98 (m, 1H). LCMS (ES, m/z): 526 [M + H]⁺. 418

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55-7.37 (m, 2H), 6.80 (s, 1H),6.77-6.72 (m, 1H), 6.66-6.59 (m, 1H), 6.15 (s, 1H), 4.85-4.70 (m, 2H),3.80 (s, 6H), 3.28-3.19 (m, 1H), 3.05-2.95 (m, 1H), 2.91-2.87 (m, 1H),2.42-2.03 (m, 5H), 1.81-1.60 (m, 3H), 1.56-1.38 (m, 2H), 1.16 (d, J =6.8 Hz, 3H). LCMS (ES, m/z): 526 [M + H]⁺. 419

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48-7.38 (m, 2H), 7.25 (s, 1H), 7.15(d, J = 8.4 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 6.11 (s, 1H), 4.81-4.74(m, 2H), 4.53 (t, J = 8.8 Hz, 2H), 3.79 (s, 3H), 3.29-3.25 (m, 1H),3.19-3.14 (m, 2H), 3.03-2.91 (m, 2H), 2.36-2.25 (m, 2H), 2.15-2.07 (m,3H), 1.77-1.60 (m, 3H), 1.35-1.25 (m, 2H), 1.16 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 520 [M + H]⁺. 420

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53-7.39 (m, 2H), 7.17-7.05 (m, 3H),6.14 (s, 1H), 4.89-4.67 (m, 2H), 3.86 (s, 3H), 3.79 (s, 3H), 3.32-3.21(m, 1H), 3.04-2.93 (m, 1H), 2.91-2.89 (s, 1H), 2.40-2.22 (m, 2H),2.22-2.10 (m, 2H), 2.10-2.05 (m, 1H), 1.81-1.60 (m, 3H), 1.52-1.40 (m,2H), 1.16 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 526 [M + H]⁺. 421

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52-7.42 (m, 2H), 7.00-6.89 (m, 3H),6.13 (s, 1H), 4.85-4.73 (m, 2H), 3.81 (s, 3H), 3.79 (s, 3H), 3.33-3.22(m, 1H), 3.04-2.90 (m, 2H), 2.42-2.22 (m, 2H), 2.16-2.07 (m, 3H),1.78-1.54 (m, 3H), 1.48-1.32 (m, 2H), 1.17 (d, J = 6.8 Hz, 3H). LCMS(ES, m/z): 542 [M + H]⁺. 422

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.96-7.95 (m, 1H), 7.54-7.43 (m, 2H),7.33 (d, J = 8.8 Hz, 1H), 7.20 (d, J = 8.4 Hz, 1H), 6.63-6.56 (m, 1H),5.56-5.39 (m, 1H), 4.79-4.64 (m, 1H), 3.76 (s, 3H), 3.28-3.17 (m, 1H),2.96-2.79 (m, 2H), 2.47-2.14 (m, 5H), 1.92-1.81 (m, 3H), 1.81-1.61 (m,3H), 1.41-1.19 (m, 3H), 1.11 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 504[M + H]⁺. 423

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47-7.30 (m, 6H), 6.22 (s, 1H),4.92-4.90 (m, 1H), 4.78-4.74 (m, 1H), 3.78 (m, 3H), 3.33-3.24 (m, 1H),3.01-2.82 (m, 2H), 2.34-2.14 (m, 5H), 1.76-1.38 (m, 5H), 1.16 (d, J =6.4 Hz, 3H). LCMS (ES, m/z): 512 [M + H]⁺. 424

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56-7.47 (m, 1H), 7.47-7.31 (m, 1H),7.21-7.09 (m, 1H), 7.09-6.89 (m, 2H), 6.53 (s, 1H), 4.81-4.61 (m, 2H),3.85 (s, 3H), 3.78 (s, 3H), 3.31-3.18 (m, 1H), 3.06-2.82 (m, 2H),2.57-2.41 (m, 1H), 2.41-2.31 (m, 1H), 2.31-2.09 (m, 3H), 1.83-1.58 (m,3H), 1.49-1.21 (m, 2H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 526[M + H]⁺ 425

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.42-7.28 (m, 2H), 7.22-7.10 (m, 5H),5.08 (d, J = 9.2 Hz, 1H), 4.79-4.75 (m, 1H), 4.39-4.35 (m, 1H), 3.78 (s,3H), 3.65-.3.53 (m, 1H), 3.26-3.20 (m, 1H), 3.05-2.96 (m, 2H), 2.42-2.20(m, 1H), 2.20-1.92 (m, 4H), 1.79-1.70 (m, 1H), 1.70-1.50 (m, 5H),1.40-1.35 (m, 1H), 1.14 (d, J = 6.8 Hz, 3H), 0.58-0.56 (m, 1H). LCMS(ES, m/z): 506 [M + H]⁺ 426

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52-7.51 (m, 2H), 7.23-7.13 (m, 2H),6.10 (s, 1H), 4.85-4.70 (m, 2H), 4.63 (t, J = 8.4 Hz, 2H), 3.79 (s, 3H),3.31-3.19 (m, 3H), 3.04-2.88 (m, 2H), 2.43-2.21 (m, 2H), 2.20-2.05 (m,3H), 1.80-1.59 (m, 3H), 1.45-1.30 (m, 2H), 1.16 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 554 [M + H]⁺. 427

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51-7.41 (m, 1H), 7.41-7.29 (m, 1H),7.24-7.13 (m, 1H), 7.11-6.94 (m, 1H), 6.19 (s, 1H), 4.95-4.91 (m, 1H),4.81-4.71 (m, 1H), 4.63 (t, J = 8.8 Hz, 2H), 3.78 (s, 3H), 3.32-3.18 (m,3H), 3.08-2.91 (m, 1H), 2.82-2.67 (m, 1H), 2.39-2.18 (m, 4H), 2.16-1.98(m, 1H), 1.82-1.68 (m, 1H), 1.68-1.50 (m, 2H), 1.50-1.38 (m, 1H), 1.16(d, J = 6.8 Hz, 3H), 1.14-1.06 (m, 1H). LCMS (ES, m/z): 538 [M + H]⁺ 428

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58-7.44 (m, 1H), 7.44-7.34 (m, 1H),7.31-7.19 (m, 1H), 6.96-6.78 (m, 1H), 6.57 (s, 1H), 4.81-4.66 (m, 1H),4.52-4.29 (m, 1H), 3.87 (s, 3H), 3.79 (s, 3H), 3.33-3.21 (m, 1H),3.08-2.84 (m, 2H), 2.59-2.41 (m, 1H), 2.39-2.22 (m, 2H), 2.22-2.12 (m,1H), 2.12-1.96 (m, 1H), 1.82-1.68 (m, 1H), 1.69-1.52 (m, 2H), 1.24-1.07(m, 4H), 1.24-0.99 (m, 1H). LCMS (ES, m/z): 544 [M + H]⁺ 429

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.06 (s, 1H), 7.56-7.50 (m, 1H),7.48-7.39 (m, 2H), 7.16-7.08 (m, 1H), 6.59 (s, 1H), 5.06-4.95 (m, 1H),4.82-4.73 (m, 1H), 3.79 (s, 3H), 3.31-3.22 (m, 1H), 3.05-2.92 (m, 2H),2.47-2.10 (m, 5H), 1.82-1.64 (m, 3H), 1.5-1.28 (m, 2H), 1.17 (d, J = 6.8Hz, 3H). LCMS (ES, m/z): 536 [M + H]⁺. 430

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.74 (d, J = 9.2 Hz, 1H), 7.52 (d, J =8.8 Hz, 1H), 7.41 (d, J = 8.8 Hz, 1H), 6.99-6.97 (m, 2H), 6.40 (s, 1H),4.85-4.81 (m, 1H), 4.74-4.71 (m, 1H), 3.82 (s, 3H), 3.78 (s, 3H),3.20-3.13 (m, 1H), 2.95-2.90 (m, 1H), 2.89-2.85 (m, 1H), 2.47-2.45 (m,1H), 2.30-2.17 (m, 4H), 1.75-1.64 (m, 4H), 1.54-1.45 (m, 1H), 1.14 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 542 [M + H]⁺. 431

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.59 (d, J = 9.2 Hz, 1H), 7.41 (d, J =9.2 Hz, 1H), 7.24 (d, J = 8.8 Hz, 1H), 7.02 (s, 1H), 6.84 (d, J = 8.8Hz, 1H), 6.50 (s, 1H), 4.77-4.72 (m, 1H), 4.54-4.53 (m, 1H), 3.80 (s,3H), 3.79 (s, 3H), 3.29-3.23 (m, 1H), 2.98-2.91 (m, 2H), 2.47-2.45 (m,1H), 2.36-2.33 (m, 1H), 2.28-2.17 (m, 2H), 2.08-2.03 (m, 1H), 1.72-1.65(m, 3H), 1.37-1.21 (m, 1H), 1.21-1.18 (m, 1H), 1.15 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 542 [M + H]⁺. 432

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.51 (d, J = 9.0 Hz, 1H), 7.44 (d, J =9.0 Hz, 1H), 7.40-7.31 (m, 1H), 7.23-7.18 (m, 1H), 7.15-7.11 (m, 1H),6.18 (s, 1H), 4.93-4.91 (m, 1H), 4.80-4.76 (m, 1H), 3.79 (s, 3H),3.26-3.21 (m, 1H), 3.01-2.94 (m, 1H), 2.86-2.84 (m, 1H), 2.41-2.09 (m,4H), 1.92-1.89 (m, 1H), 1.78-1.48 (m, 5H), 1.16 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 514 [M + H]⁺. 433

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.62-7.51 (m, 2H), 7.12-7.07 (m, 1H),7.03-6.97 (m, 1H), 6.86-6.80 (m, 1H), 6.20 (s, 1H), 5.03-4.92 (m, 1H),4.78 (m, 1H), 3.81 (s, 3H), 3.79 (s, 3H), 3.24-3.22 (m, 1H), 3.06-2.96(m, 2H), 2.53-2.36 (m, 2H), 2.32-2.28 (m, 1H), 2.14-2.12 (m, 1H),2.04-2.00 (m, 1H), 1.83-1.71 (m, 1H), 1.61-1.52 (m, 2H), 1.40-1.31 (m,1H), 1.16 (d, J = 6.8 Hz, 3H), 1.05-0.97 (m, 1H). LCMS (ES, m/z): 542[M + H]⁺. 434

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.87-7.74 (m, 2H), 7.43-7.30 (m, 2H),7.02-6.92 (m, 1H), 6.76 (s, 1H), 6.59-6.52 (m, 1H), 4.86-4.71 (m, 2H),3.82 (s, 3H), 3.29-3.09 (m, 2H), 3.06-2.97 (m, 1H), 2.47-2.36 (m, 2H),2.35-2.24 (m, 1H), 2.16-2.08 (m, 1H), 2.05-1.85 (m, 2H), 1.74-1.60 (m,1H), 1.59-1.45 (m, 1H), 1.20 (d, J = 6.8 Hz, 3H), 0.93-0.77 (m, 1H),0.75-0.61 (m, 1H). LCMS (ES, m/z): 535 [M + H]⁺. 435

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.21-8.01 (m, 1H), 7.79-7.62 (m, 1H),7.56-7.44 (m, 1H), 7.44-7.33 (m, 1H), 7.33-7.16 (m, 1H), 7.03-6.88 (m,1H), 5.52-5.31 (m, 1H), 4.81-4.61 (m, 1H), 3.76 (s, 3H), 3.31-3.12 (m,1H), 3.02-2.87 (m, 2H), 2.59-2.41 (m, 1H), 2.35-2.12 (m, 4H), 2.04-1.92(m, 1H), 1.91-1.59 (m, 6H), 1.47-1.31 (m, 2H), 1.14 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 505 [M + H]⁺. 436

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.87 (s, 1H), 7.57 (d, J = 8.8 Hz, 1H),7.52-7.38 (m, 2H), 5.51-5.44 (m, 1H), 5.36-5.25 (m, 1H), 5.03-4.92 (m,1H), 4.82-4.71 (m, 1H), 4.60-4.52 (m, 1H), 3.79 (s, 3H), 3.24-3.11 (m,1H), 3.09-2.86 (m, 2H), 2.49-2.19 (m, 4H), 1.96-1.85 (m, 2H), 1.80-1.60(m, 3H), 1.36-1.29 (m, 1H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):516 [M + H]⁺. 437

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.64-7.39 (m, 3H), 7.39-7.21 (m, 1H),7.16-6.89 (m, 1H), 6.17 (s, 1H), 5.03-4.91 (m, 1H), 4.82-4.68 (m, 1H),3.87 (s, 3H), 3.78 (s, 3H), 3.29-3.12 (m, 1H), 3.02-2.89 (m, 2H),2.51-2.21 (m, 3H), 2.19-1.93 (m, 2H), 1.84-1.71 (m, 1H), 1.69-1.54 (m,2H), 1.51-1.36 (m, 1H), 1.16 (d, J = 6.4 Hz, 3H), 1.10-0.97 (m, 1H).LCMS (ES, m/z): 542 [M + H]⁺ 438

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52-7.40 (m, 2H), 7.32-7.24 (m, 1H),7.16-7.10 (m, 1H), 7.08-7.00 (m, 1H), 6.17 (s, 1H), 4.98-4.90 (m, 1H),4.82-4.71 (m, 1H), 3.86 (s, 3H), 3.79 (s, 3H), 3.30-3.17 (m, 1H),3.04-2.94 (m, 2H), 2.50-2.29 (m, 2H), 2.27-2.18 (m, 1H), 2.13-1.95 (m,2H), 1.80-1.68 (m, 1H), 1.61-1.54 (m, 2H), 1.44-1.27 (m, 1H), 1.15 (d, J= 6.8, 3H), 1.09-1.06 (m, 1H). LCMS (ES, m/z): 526 [M + H]⁺. 439

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52-7.50 (m, 1H), 7.43-7.40 (m, 1H),7.40-7.37 (m, 2H), 7.32-7.30 (m, 3H), 6.89 (s, 1H), 4.81-4.78 (m, 1H),4.52-4.48 (m, 1H), 3.79 (s, 3H), 3.30-3.18 (m, 1H), 3.10-2.94 (m, 1H),2.40-2.20 (m, 2H), 2.18-2.09 (m, 6H), 1.82-1.76 (m, 1H), 1.72-1.67 (m,2H), 1.43-1.35 (m, 1H), 1.32-1.29 (m, 1H), 1.16 (d, J = 6.7 Hz, 3H),1.12-1.03 (m, 1H). LCMS (ES, m/z): 519 [M + H]⁺. 440

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.83 (s, 2H), 7.30 (d, J = 6.8 Hz, 1H),7.23 (d, J = 8.0 Hz, 1H), 6.93 (t, J = 7.6 Hz, 1H), 6.42 (s, 1H),4.85-4.62 (m, 3H), 4.53-4.41 (m, 1H), 3.833 (s, 3H), 3.27-2.98 (m, 5H),2.53-2.35 (m, 2H), 2.34-2.09 (m, 3H), 1.92-1.85 (m, 1H), 1.75-1.62 (m,2H), 1.22-1.01 (m, 5H). LCMS (ES, m/z): 520 [M + H]⁺ 441

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.30 (d, J = 8.8 Hz, 1H), 7.18 (d, J =8.8 Hz, 1H), 7.10-6.96 (m, 2H), 6.83-6.73 (m, 1H), 4.82-4.68 (m, 1H),4.21-4.05 (m, 1H), 3.82-3.69 (m, 5H), 3.62-3.49 (m, 3H), 3.30-3.12 (m,2H), 3.11-3.02 (m, 1H), 2.99-2.87 (m, 1H), 2.35-2.01 (m, 5H), 1.76-1.64(m, 3H), 1.57-1.45 (m, 4H), 1.12 (d, J = 6.8 Hz, 3H), 0.92-0.71 (m, 1H).LCMS (ES, m/z): 523 [M + H]⁺. 442

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.59-7.47 (m, 1H), 7.47-7.32 (m, 2H),7.12-6.99 (m, 1H), 7.09-6.93 (m, 1H), 6.51 (s, 1H), 4.82-4.57 (m, 2H),3.87 (s, 3H), 3.78 (s, 3H), 3.32-3.18 (m, 1H), 3.05-2.79 (m, 2H),2.57-2.41 (m, 1H), 2.41-2.31 (m, 1H), 2.31-2.05 (m, 3H), 1.82-1.67 (m,3H), 1.52-1.22 (m, 2H), 1.16 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 542[M + H]⁺ 443

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.81-7.75 (m, 3H), 7.34 (s, 1H),4.87-4.72 (m, 2H), 4.71-4.62 (m, 2H), 4.30-4.15 (m, 1H), 3.79 (s, 3H),3.18-2.96 (m, 3H), 2.45-2.20 (m, 5H), 1.95-1.70 (m, 3H), 1.65-1.60 (m,1H), 1.62 (d, J = 6.8 Hz, 3H), 1.55-1.40 (m, 1H), 1.16 (d, J = 6.4 Hz,3H). LCMS (ES, m/z): 514 [M + H]⁺. 444

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.86-7.83 (m, 3H), 7.51-7.34 (m, 2H),7.29-7.23 (m, 1H), 6.64-6.62 (m, 1H), 4.89-4.76 (m, 3H), 3.83 (s, 3H),3.27-3.02 (m, 3H), 2.48-2.14 (m, 5H), 1.90-1.85 (m, 1H), 1.76-1.69 (m,2H), 1.27-1.15 (m, 5H). LCMS (ES, m/z): 546 [M + H]⁺. 445

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58-7.52 (m, 1H), 7.45-7.40 (m, 1H),7.31-7.29 (m, 1H), 7.08-6.90 (m, 2H), 6.38 (s, 1H), 4.86-4.75 (m, 2H),4.62-4.50 (m, 1H), 3.79 (s, 3H), 3.30-3.17 (m, 1H), 2.95-2.86 (m, 2H),2.48-2.44 (m, 1H), 2.32-2.24 (m, 4H), 1.80-1.50 (m, 5H), 1.18 (d, J =6.0 Hz, 3H), 1.13 (d, J = 6.4 Hz, 3H), 1.03 (d, J = 6.0 Hz, 3H). LCMS(ES, m/z): 554 [M + H]⁺. 446

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56-7.54 (m, 1H), 7.44-7.41 (m, 1H),7.20-7.04 (m, 3H), 4.80-4.70 (m, 1H), 4.65-4.50 (m, 1H), 4.35-4.25 (m,1H), 4.05-3.95 (m, 2H), 3.80-3.50 (m, 5H), 3.40-3.10 (m, 3H), 2.98-2.85(m, 1H), 2.55-2.15 (m, 6H), 1.95-1.65 (m, 3H), 1.12 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 510 [M + H]⁺ 447

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.78 (d, J = 9.2 Hz, 1H), 7.59 (d, J =9.2 Hz, 1H), 7.49-7.32 (m, 1H), 7.30-7.16 (m, 2H), 5.30-5.14 (m, 1H),4.84-4.74 (m, 1H), 4.34-4.25 (m, 1H), 4.02-3.90 (m, 1H), 3.82 (s, 3H),3.62-3.49 (m, 1H), 3.13-2.92 (m, 2H), 2.41-2.32 (m, 1H), 2.28-2.02 (m,5H), 2.02-1.95 (m, 1H), 1.95-1.82 (m, 3H), 1.16 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 498 [M + H]⁺. 448

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.87-7.76 (m, 2H), 7.42 (s, 1H),7.32-7.22 (m, 1H), 6.85-6.74 (m, 2H), 6.54-6.51 (m, 1H), 5.27-5.16 (m,1H), 4.85-4.76 (m, 1H), 3.82 (s, 3H), 3.20-3.03 (m, 2H), 3.02-2.93 (m,1H), 2.54-2.33 (m, 2H), 2.32-2.20 (m, 1H), 2.14-1.86 (m, 3H), 1.70-1.56(m, 1H), 1.55-1.44 (m 1H), 1.19 (d, J = 6.8 Hz, 3H), 1.05-0.81 (m, 2H).LCMS (ES, m/z): 535 [M + H]⁺. 449

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55-7.50 (m, 1H), 7.43-7.41 (m, 1H),7.36-7.32 (m, 1H), 7.14-7.08 (m, 2H), 6.42 (s, 1H), 4.87-4.72 (m, 2H),3.78 (s, 3H), 3..33-3.20 (m, 1H), 2.96-2.88 (m, 2H), 2.47-2.2.42 (m,1H), 2.32-2.12 (m, 4H), 1.80-1.67 (m, 3H), 1.59-1.48 (m, 2H), 1.15 (d, J= 6.4 Hz, 3H). LCMS (ES, m/z): 514 [M + H]⁺ 450

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.22 (s, 1H), 7.99-7.90 (m, 1H),7.82-7.73 (m, 1H), 7.71-7.62 (m, 1H), 7.51-7.37 (m, 2H), 7.23-7.12 (m,1H), 5.40-5.25 (m, 1H), 4.73-4.62 (m, 1H), 3.67 (s, 3H), 3.18-3.02 (m,1H), 3.02-2.86 (m, 1H), 2.58-2.50 (m, 1H), 2.24-1.88 (m, 9H), 1.80-1.68(m, 1H), 1.66-1.44 (m, 3H), 1.38-1.29 (m, 1H), 1.05 (d, J = 6.6, 3H).LCMS (ES, m/z): 528 [M + H]⁺. 451

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.68 (s, 1H), 7.50 (d, J = 8.4 Hz, 1H),7.49-7.40 (m, 3H), 6.32 (s, 1H), 4.89-4.74 (m, 2H), 3.79 (s, 3H),3.29-3.25 (m, 1H), 3.04-2.98 (m, 1H), 2.85-2.83 (m, 1H), 2.64 (s, 3H),2.35-2.31 (m, 2H), 2.29-2.26 (m, 2H), 2.13-1.97 (m, 1H), 1.78-1.74 (m,1H), 1.67-1.61 (m, 2H), 1.44-1.20 (m, 2H), 1.17 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 533 [M + H]⁺. 452

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.54 (d, J = 8.8 Hz, 1H), 7.47-7.42 (m,2H), 7.40-7.12 (m, 2H), 6.85-6.45 (m, 1H), 6.44 (s, 1H), 4.94-4.91 (m,1H), 4.76-4.71 (m, 1H), 3.78 (s, 3H), 3.22-2.84 (m, 3H), 2.46-2.23 (m,5H), 1.84-1.61 (m, 5H), 1.14 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 562[M + H]⁺. 453

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55 (d, J = 8.8 Hz, 1H), 7.38 (d, J =8.8 Hz, 1H), 7.28-7.15 (m, 5H), 5.73-5.54 (m, 1H), 4.78-7.64 (m, 1H),3.80 (s, 3H), 3.51-3.33 (m, 2H), 3.28-3.17 (m, 2H), 3.02-2.83 (m, 2H),2.64-2.52 (m, 1H), 2.45-2.21 (m, 4H), 1.91-1.80 (m, 2H), 1.75-1.62 (m,5H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 506 [M + H]⁺. 454

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55 (d, J = 9.2 Hz, 1H), 7.41 (d, J =8.8 Hz, 1H), 5.27-5.12 (m, 2H), 4.80-4.76 (m, 1H), 3.79 (s, 3H),3.23-3.16 (m, 1H), 3.08-2.88 (m, 2H), 2.58-2.53 (m, 1H), 2.39-2.19 (m,5H), 1.98-1.88 (m, 4H), 1.75-1.66 (m, 6H), 1.53-1.48 (m, 2H), 1.33-1.18(m, 3H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 484 [M + H]⁺. 455

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46-7.38 (m, 2H), 7.30-7.25 (m, 5H),4.75-4.74 (m, 1H), 4.50-4.46 (m, 1H), 4.26-4.25 (m, 1H), 3.76-3.74 (m,4H), 3.69-3.63 (m, 1H), 3.41-3.35 (m, 4H), 3.11-3.09 (m, 1H), 2.94-2.90(m, 1H), 2.27-2.09 (m, 3H), 2.00-1.96 (m, 1H), 1.75-1.72 (m, 1H),1.61-1.48 (m, 3H), 1.29-1.25 (m, 1H), 1.11 (d, J = 6.8 Hz, 3H),1.07-1.05 (m, 1H). LCMS (ES, m/z): 506 [M + H]+. 456

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58-7.52 (m, 1H), 7.48-7.39 (m, 5H),5.05-4.91 (m, 1H), 4.85-4.72 (m, 1H), 4.35-4.20 (m, 1H), 3.85-3.73 (m,4H), 3.44-3.35 (m, 1H), 3.15-3.02 (m, 1H), 2.98-2.85 (m, 1H), 2.31-1.95(m, 6H), 1.90-1.68 (m, 4H), 1.12 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):496 [M + H]⁺. 457

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53-7.38 (m, 1H), 7.38-7.23 (m, 2H),6.03 (s, 1H), 4.83-4.68 (m, 1H), 4.68-4.51 (m, 1H), 4.51-4.36 (m, 1H),4.36-4.17 (m, 1H), 4.03-3.88 (m, 1H), 3.76 (s, 3H), 3.27-3.09 (m, 1H),3.01-2.82 (m, 1H), 2.59-2.07 (m, 6H), 1.99-1.59 (m, 4H), 1.59-1.39 (m,4H), 1.14-1.12 (d, J = 6.6 Hz, 3H). LCMS: (ES, m/z): 514 [M + H]⁺. 458

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.49 (s, 1H), 7.85-7.77 (m, 1H), 7.67(d, J = 8.4 Hz, 1H), 7.59-7.51 (m, 1H), 7.50-7.45 (m, 1H), 7.44-7.37 (m,1H), 6.35 (s, 1H), 4.88-4.83 (m, 1H), 4.81-4.73 (m, 1H), 3.79 (s, 3H),3.30-3.24 (m, 1H), 3.07-2.93 (m, 1H), 2.86-2.77 (m, 1H), 2.41-2.23 (m,2H), 2.21-2.05 (m, 2H), 2.03-1.90 (m, 1H), 1.83-1.71 (m, 1H), 1.70-1.53(m, 2H), 1.52-1.29 (m, 2H), 1.17 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):519 [M + H]⁺. 459

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.93-7.66 (m, 2H), 7.66-7.46 (m, 1H),6.17 (s, 1H), 4.83-4.72 (m, 1H), 4.72-4.53 (m, 2H), 4.33-4.09 (m, 1H),3.80 (s, 3H), 3.18-2.88 (m, 3H), 2.59-2.13 (m, 5H), 1.99-1.66 (m, 4H),1.63 (d, J = 7.2 Hz, 3H), 1.59-1.40 (m, 1H), 1.34-1.23 (m, 1H), 1.15 (d,J = 6.6 Hz, 3H). LCMS (ES, m/z): 514 [M + H]⁺. 460

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.4-7.33 (m, 2H), 7.34 (s, 1H), 7.15(d, J = 8.0 Hz, 1H), 6.68 (d, J = 8.0 Hz, 1H), 6.18 (s, 1H), 4.94-4.88(m, 1H), 4.79-4.75 (m, 1H), 4.53 (t, J = 8.4 Hz, 2H), 3.78 (s, 3H),3.25-3.15 (m, 3H), 3.01-2.92 (m, 2H), 2.43-2.30 (m, 3H), 2.28-1.98 (m,2H), 1.78-1.73 (m, 1H), 1.64-1.58 (m, 2H), 1.40-1.31 (m, 1H), 1.15 (d, J= 6.8 Hz, 3H), 1.07-1.04 (m, 1H). LCMS (ES, m/z): 520 [M + H]⁺. 461

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.57-7.42 (m, 2H), 7.29 (s, 1H), 7.22(s, 1H), 6.18 (s, 1H), 5.08-4.93 (m, 1H), 4.83-4.71 (m, 1H), 4.63 (t, J= 8.4 Hz, 2H), 3.79 (s, 3H), 3.30-3.12 (m, 3H), 3.04-2.90 (m, 2H),2.51-2.38 (m, 1H), 2.39-2.20 (m, 2H), 2.16-1.98 (m, 2H), 1.82-1.71 (m,1H), 1.70-1.62 (m, 2H), 1.54-1.39 (m, 1H), 1.16 (d, J = 6.4 Hz, 3H),1.14-1.09 (m, 1H). LCMS (ES, m/z): 554 [M + H]⁺. 462

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51-7.25 (m, 7H), 6.20 (s, 1H),4.98-4.72 (m, 2H), 3.79 (s, 3H), 3.33-3.25 (m, 1H), 3.06-2.81 (m, 2H),2.41-2.20 (m, 2H), 2.18-2.05 (m, 3H), 1.81-1.72 (m, 1H), 1.70-1.53 (m,2H), 1.48-1.25 (m, 2H), 1.16 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 478[M + H]⁺. 463

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.68-7.66 (m, 2H), 7.10-6.96 (m, 3H),4.85-4.75 (m, 2H), 4.54-4.38 (m, 2H), 3.82 (s, 3H), 3.80 (s, 3H),3.16-3.12 (m, 1H), 3.06-2.94 (m, 2H), 2.44-2.39 (m, 1H), 2.34-2.11 (m,4H), 1.84-1.65 (m, 3H), 1.33-1.25 (m, 2H), 1.17 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 510 [M + H]⁺ 464

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49-7.41 (m, 2H), 7.17-7.12 (m, 1H),6.77-6.74 (m, 1H), 6.55 (s, 1H), 4.86-4.76 (m, 1H), 4.38-4.34 (m, 1H),3.84 (s, 3H), 3.79 (s, 3H), 3.53 (s, 3H), 3.33-325 (m, 1H), 3.05-2.98(m, 1H), 2.94-2.92 (m, 1H), 2.50-2.48 (m, 1H), 2.31-2.18 (m, 3H),2.02-1.93 (m, 1H), 1.79-1.75 (m, 1H), 1.61-1.58 (m, 2H), 1.18-1.16 (m,4H), 0.99-0.96 (m, 1H). LCMS (ES, m/z): 556 [M + H]⁺ 465

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.46 (s, 1H), 8.89 (s, 2) 8.86 (s, 1H),7.78 (d, J = 3.6 Hz, 1H), 5.13-5.02 (m, 1H), 4.97 (d, J = 6.8 Hz, 2H),4.87-4.81 (m, 1H), 3.84 (s, 3H), 3.33-2.99 (m, 3H), 2.45-2.15 (m, 5H),1.88-1.70 (m, 4H), 1.43-1.28 (m, 1H), 1.19 (d, J = 6.8 Hz, 3H). LCMS(ES, m/z): 503 [M + H]⁺. 466

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53-7.41 (m, 2H), 7.18-7.06 (m, 3H),4.85-4.70 (m, 1H), 4.60-4.50 (m, 1H), 4.12-4.00 (m, 1H), 3.85 (s, 3H),3.78 (s, 3H), 3.12-2.75 (m, 2H), 2.55-1.65 (m, 9H), 1.60-1.45 (m, 1H),1.40-1.25 (m, 1H), 1.18 (d, J = 6.9 Hz, 3H), 1.18-1.10 (m, 4H), 0.93 (d,J = 6.6 Hz, 3H). LCMS (ES, m/z): 552 [M + H]⁺ 467

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.61 (s, 1H), 7.45-7.38 (m, 3H),7.38-7.32 (m, 1H), 7.17-7.15 (m, 1H), 6.42 (s, 1H), 6.41 (s, 1H),4.91-4.75 (m, 2H), 3.79 (s, 3H), 3.78 (s, 3H), 3.31-3.22 (m, 1H),3.11-3.00 (m, 1H), 2.91-2.85 (m, 1H), 2.45-2.31 (m, 2H), 2.28-2.21 (m,1H), 2.12-2.00 (m, 1H), 1.99-1.80 (m, 1H), 1.79-1.70 (m, 1H), 1.62-1.40(m, 2H), 1.17 (d, J = 6.4 Hz, 3H), 1.12-1.09 (m, 1H), 0.92-0.89 (m, 1H).LCMS (ES, m/z): 531 [M + H]⁺. 468

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.85-7.76 (m, 4H), 7.56-7.53 (m, 1H),7.49-7.43 (m, 3H), 7.37-7.34 (m, 1H), 4.87-4.72 (m, 1H), 4.60-4.56 (m,1H), 4.50-4.45 (m, 1H), 3.94-3.70 (m, 6H), 3.51-3.50 (m, 1H), 3.45-3.38(m, 1H), 3.22-3.11 (m, 2H), 2.94 (m, 1H), 2.60-2.05 (m, 3H), 2.00-1.71(m, 3H), 1.12 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 528 [M + H]⁺ 469

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.50-7.48 (m, 1H), 7.41-7.37 (m, 1H),7.307-7.01 (m, 5H), 5.65-5.50 (m, 1H), 5.05-4.96 (m, 1H), 4.80-4.69 (m,1H), 3.79 (s, 3H), 3.50-3.35 (m, 1H), 3.30-3.15 (m, 2H), 2.99-2.82 (m,2H), 2.35-2.22 (m, 4H), 1.94-1.80 (m, 6H), 1.79-1.60 (m, 3H), 1.16 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 533 [M + H]⁺. 470

¹H-NMR (DMSO, 400 MHz) δ (ppm): 7.49-7.45 (m, 1H), 7.32-7.27 (m, 3H),6.89-6.86 (m, 2H), 6.50-6.20 (m, 1H), 6.03 (s, 1H), 4.86-4.79 (m, 1H),4.67-4.62 (m, 1H), 3.72 (s, 3H), 3.67 (s, 3H), 3.08-3.01 (m, 1H),2.88-2.82 (m, 2H), 2.34-2.29 (m, 1H), 2.18-2.10 (m, 2H), 1.95-1.88 (m,2H), 1.66-1.61 (m, 1H), 1.58-1.48 (m, 2H), 1.26-1.22 (m, 1H), 1.06 (d, J= 6.8 Hz, 3H), 1.94-0.90 (m, 1H). LCMS (ES, m/z): 508 [M + H]⁺. 471

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46 (d, J = 8.8 Hz, 1H), 7.39 (d, J =8.8 Hz, 1H), 7.19-7.10 (m, 1H), 6.97-6.87 (m, 2H), 4.81-4.62 (m, 2H),4.42-4.23 (m, 2H), 3.76 (s, 3H), 3.25-3.10 (m, 1H), 3.02-2.88 (m, 2H),2.37-2.06 (m, 8H), 1.81-1.59 (m, 3H), 1.34-1.20 (m, 2H), 1.13 (d, J =6.4 Hz, 3H). LCMS (ES, m/z): 494 [M + H]⁺. 472

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.50-7.40 (m, 2H), 7.27-7.08 (m, 2H),6.94-6.84 (m, 2H), 6.23 (s, 1H), 4.91-4.88 (m, 1H), 3.79 (s, 6H),3.34-2.96 (m, 2H), 2.78-2.68 (m, 1H), 2.36-2.05 (m, 5H), 1.78-1.55 (m,3H), 1.31-1.15 (m, 6H). LCMS (ES, m/z): 508 [M + H]⁺. 473

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53-7.24 (m, 7H), 5.80 (s, 1H),4.80-4.72 (m, 2H), 3.79 (s, 3H), 3.52 (s, 3H), 3.32-3.25 (m, 1H),3.05-2.86 (m, 2H), 2.38-2.19 (m, 2H), 2.18-2.02 (m, 3H), 1.78-1.55 (m,3H), 1.52-1.30 (m, 2H), 1.17 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 492[M + H]⁺. 474

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58-7.46 (m, 1H), 7.46-7.37 (m, 1H),7.17-7.01 (m, 2H), 6.15 (s, 1H), 5.03-4.92 (m, 1H), 4.83-4.71 (m, 1H),4.63 (t, J = 8.4 Hz, 2H), 3.78 (s, 3H), 3.31-3.18 (m, 3H), 3.02-2.83 (m,2H), 2.52-2.31 (m, 2H), 2.31-2.21 (m, 1H), 2.16-2.08 (m, 1H), 2.08-1.98(m, 1H), 1.84-1.69 (m, 1H), 1.69-1.51 (m, 2H), 1.47-1.33 (m, 1H), 1.15(d, J = 6.8 Hz, 3H), 1.12-1.04 (m, 1H). LCMS (ES, m/z): 538 [M + H]⁺ 475

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49-7.47 (m, 1H), 7.40-7.37 (m, 3H),7.34-7.25 (m, 3H), 4.77-4.71 (m, 2H), 4.32-4.30 (m, 1H), 3.76-3.66 (m,5H), 3.39 (s, 3H), 3.27-3.22 (m, 1H), 3.13-3.10 (m, 1H), 2.92-2.87 (m,1H), 2.38-2.21 (m, 3H), 2.08-2.04 (m, 1H), 1.96-1.86 (m, 3H), 1.74-1.69(m, 2H), 1.55-1.50 (m, 1H), 1.12 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):506 [M + H]+. 476

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.15-8.12 (m, 1H), 7.75-7.71 (m, 1H),7.58-7.55 (m, 2H), 7.47-7.44 (m, 1H), 6.71-6.69 (m, 1H), 6.10-6.06 (m,1H), 5.70-5.66 (m, 1H), 5.15-5.06 (m, 1H), 4.78-4.74 (m, 1H), 3.78 (s,3H), 3.22-3.14 (m, 1H), 2.98-2.90 (m, 2H), 2.43-2.37 (m, 1H), 2.32-2.20(m, 4H), 1.74-1.68 (m, 3H), 1.54-1.46 (m, 2H), 1.14 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 527 [M + H]⁺. 477

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.50-7.30 (m, 2H), 7.12-6.93 (m, 3H),4.80-4.70 (m, 1H), 4.64-4.53 (m, 1H), 4.32-4.20 (m, 1H), 3.85 (s, 3H),3.78 (s, 3H), 3.04-2.89 (m, 1H), 2.49-2.23 (m, 3H), 2.23-2.05 (m, 2H),1.97 (s, 1H), 1.92-1.65 (m, 5H), 1.64-1.52 (m, 1H), 1.38-1.23 (m, 2H),1.16 (d, J = 6.8 Hz, 1H), 1.12-1.08 (m, 1H). LCMS (ES, m/z): 524 [M +H]⁺. 478

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.09 (s, 1H), 7.52-7.50 (m, 1H),7.49-7.40 (m, 2H), 7.24-7.20 (m, 1H), 6.63 (s, 1H), 5.20-5.08 (m, 1H),5.85-5.75 (m, 1H), 3.80 (s, 3H), 3.28-3.15 (m, 1H), 3.04-2.91 (m, 2H),2.48-2.41 (m, 2H), 2.34-2.25 (m, 1H), 2.15-1.95 (m, 2H), 1.80-1.45 (m,3H), 1.14 (d, J = 6.4 Hz, 3H), 1.10-1.00 (m, 1H), 0.98-0.88 (m, 1H).LCMS (ES, m/z): 536 [M + H]⁺. 479

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.54-7.38 (m, 3H), 7.22-7.14 (m, 2H),6.20 (s, 1H), 4.96-4.93 (m, 1H), 4.79-4.74 (m, 1H), 3.78 (s, 3H),3.24-3.18 (m, 1H), 3.01-2.94 (m, 2H), 2.50-2.21 (m, 3H), 2.17-1.97 (m,2H), 1.78-1.72 (m, 1H), 1.63-1.55 (m, 2H), 1.49-1.31 (m, 1H), 1.14 (d, J= 6.8 Hz, 3H), 1.09-1.04 (m, 1H). LCMS (ES, m/z): 514 [M + H]⁺. 480

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.87 (s, 1H), 7.53 (s, 1H), 7.51-7.37(m, 4H), 6.33 (s, 1H), 4.94-4.89 (m, 1H), 4.79-4.74 (m, 1H), 3.78 (s,3H), 3.32-3.27 (m, 1H), 3.04-2.98 (m, 1H), 2.97-2.84 (m, 1H), 2.33-2.25(m, 2H), 2.15-1.95 (m, 3H), 1.78-1.72 (m, 1H), 1.62-1.54 (m, 2H),1.31-1.24 (m, 1H), 1.16 (d, J = 6.4 Hz, 3H), 1.15-1.13 (m, 1H). LCMS(ES, m/z): 518 [M + H]⁺. 481

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48-7.38 (m, 2H), 7.04-7.01 (m, 3H),4.86-4.67 (m, 2H), 4.40-4.15 (m, 2H), 3.85 (s, 3H), 3.76 (s, 3H),3.30-3.10 (m, 1H), 2.99-2.89 (m, 2H), 2.48-2.05 (m, 5H), 1.85-1.65 (m,3H), 1.40-1.20 (m, 2H), 1.13 (d, J = 6.4 Hz, 3H) LCMS (ES, m/z): 510[M + H]⁺. 482

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.70-7.65 (m, 2H), 7.39-7.29 (m, 2H),7.17-7.11 (m, 1H), 6.36 (s, 1H), 4.87-4.79 (m, 2H), 3.82 (s, 3H),3.73-3.71 (m, 1H), 3.33-2.99 (m, 3H), 2.46-2.18 (m, 5H), 1.83-1.68 (m,3H), 1.46-1.22 (m, 2H), 1.17 (d, J = 6.8 Hz, 3H), 0.70-0.63 (m, 2H),0.43-0.36 (m, 2H). LCMS (ES, m/z): 552 [M + H]⁺. 483

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.35 (S, 1H), 8.16 (d, J = 4.8 Hz, 1H),7.54-7.52 (m, 2H), 7.46-7.43 (m, 1H), 7.37-7.34 (m, 1H), 6.02-5.96 (m,1H), 4.84-4.64 (m, 2H), 3.79 (s, 3H), 3.25-3.11 (m, 1H), 2.96-2.81 (m,1H), 2.60-2.10 (m, 6H), 2.09-2.01 (m, 1H), 1.91 (d, J = 6.8 Hz, 3H),1.79-1.53 (m, 4H), 1.13 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 493 [M +H]⁺. 484

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.05 (s, 1H), 7.77-7.63 (m, 1H),7.55-7.27 (m, 3H), 6.92 (d, J = 8.4 Hz, 1H), 5.12-4.95 (m, 1H),4.81-4.68 (m, 1H), 3.79 (s, 3H), 3.29-3.15 (m, 1H), 3.04-2.86 (m, 2H),2.49-2.34 (m, 1H), 2.33-2.25 (m, 1H), 2.24-2.13 (m, 3H), 1.97-1.80 (m,2H), 1.78-1.61 (m, 3H), 1.59-1.50 (m, 1H), 1.46-1.28 (m, 3H), 1.15 (d, J= 6.4 Hz, 3H). LCMS (ES, m/z): 555 [M + H]⁺. 485

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.44 (d, J = 9.0 Hz, 1H), 7.33 (d, J =9.0 Hz, 1H), 7.16 (s, 1H), 5.93-5.62 (m, 1H), 4.78-4.66 (m, 1H),4.62-4.34 (m, 3H), 3.97-3.84 (m, 1H), 3.76 (s, 3H), 3.28-3.14 (m, 1H),3.02-2.73 (m, 2H), 2.37-2.05 (m, 8H), 1.89-1.59 (m, 3H), 1.59-1.39 (m,5H), 1.13 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 494 [M + H]⁺ 486

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.57-7.56 (m, 1H), 7.43-7.41 (m, 1H),5.32-5.30 (m, 1H), 5.15-5.13 (m, 1H), 4.78-4.76 (m, 1H), 3.78 (s, 3H),3.32-3.31 (m, 1H), 3.20-3.11 (m, 1H), 2.96-2.90 (m, 2H), 2.51-2.48 (m,1H), 2.48-2.36 (m, 2H), 2.36-2.27 (m, 2H), 2.08-2.04 (m, 1H), 1.93-1.86(m, 2H), 1.72-1.61 (m, 9H), 1.56-1.51 (m, 1H), 1.38-1.25 (m, 5H), 1.14(d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 498 [M + H]⁺. 487

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.67 (s, 1H), 7.76-7.63 (m, 2H),7.62-7.54 (m, 1H), 7.54-7.46 (m, 1H), 7.32-7.21 (m, 7.00 (m, 1H),5.09-4.96 (m, 1H), 4.74-4.60 (m, 1H), 3.69 (s, 3H), 3.18-3.01 (m, 1H),2.99-2.84 (m, 1H), 2.47 (s, 1H), 2.22-2.07 (m, 5H), 2.03-1.92 (m, 4H),1.80-1.64 (m, 1H), 1.59-1.36 (m, 4H), 1.05 (d, J = 6.3, 3H). LCMS (ES,m/z): 528 [M + H]⁺. 488

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.63-7.47 (m, 2H), 7.12 (d, J = 6.8 Hz,3H), 6.90-6.87 (m, 1H), 6.26 (s, 1H), 5.04-4.93 (m, 1H), 4.81-4.78 (m,1H), 3.79 (s, 3H), 3.24-3.15 (m, 1H), 3.02-2.98 (m, 2H), 2.52-2.06 (m,5H), 1.81-1.59 (m, 3H), 1.52-1.42 (m, 1H), 1.22-1.17 (m, 1H), 1.15 (d, J= 6.4 Hz, 3H). LCMS (ES, m/z): 514 [M + H]⁺. 489

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46 (d, J = 8.8 Hz, 1H), 7.38 (d, J =9.2 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H),4.81-4.62 (m, 2H), 4.45-4.22 (m, 2H), 3.79 (s, 3H), 3.28-3.12 (m, 1H),3.00-2.86 (m, 2H), 2.35-2.10 (m, 5H), 1.81-1.61 (m, 3H), 1.33-1.20 (m,2H), 1.16 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 496 [M + H]⁺. 490

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.48-7.24 (m, 3H), 7.19-6.95 (m, 3H),4.74-4.55 (m, 2H), 4.20-3.95 (m, 3H), 3.76-3.55 (m, 5H), 3.40-3.00 (m,2H), 2.92-2.85 (m, 1H), 2.55-2.05 (m, 3H), 1.87-1.68 (m, 4H), 1.10 (d, J= 6.9 Hz, 3H). LCMS (ES, m/z): 496 [M + H]⁺ 491

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.65-7.49 (m, 1H), 7.48-7.23 (m, 1H),5.33-5.12 (m, 1H), 4.82-4.58 (m, 2H), 3.78 (s, 3H), 3.28-3.12 (m, 1H),3.04-2.86 (m, 2H), 2.59-2.41 (m, 2H), 2.41-2.19 (m, 5H), 2.02-1.82 (m,2H), 1.82-1.53 (m, 9H), 1.53-1.41 (m, 3H), 1.25-1.11 (m, 5H). LCMS (ES,m/z): 498 [M + H]⁺. 492

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.75 (s, 1H), 7.62 (s, 1H), 7.44-7.33(m, 2H), 6.85-6.48 (m, 1H), 4.79-4.46 (m, 4H), 4.12-3.86 (m, 1H), 3.76(s, 3H), 3.28-3.12 (m, 1H), 3.02-2.84 (m, 2H), 2.44-2.11 (m, 5H),1.88-1.62 (m, 3H), 1.59-1.40 (m, 5H), 1.13-1.11 (d, J = 6.6 Hz, 3H).LCMS (ES, m/z): 530 [M + H]⁺. 493

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.67-7.45 (m, 2H), 7.02 (d, J = 6.4 Hz,3H), 6.94-6.91 (m, 1H), 6.23 (s, 1H), 4.93-4.92 (m, 1H), 4.81-4.79 (m,1H), 3.80 (s, 3H), 3.28-3.18 (m, 1H), 3.01-2.88 (m, 2H), 2.42-2.12 (m,4H), 2.03-1.99 (m, 1H), 1.83-1.63 (m, 4H), 1.52-1.42 (m, 1H), 1.17 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 514 [M + H]⁺. 494

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46-7.24 (m, 4H), 7.20 (d, J = 3.2 Hz,1H), 6.99 (d, J = 8.0 Hz, 1H), 6.37 (s, 1H), 4.77-4.67 (m, 1H), 4.44 (s,2H), 4.40-4.25 (m, 1H), 3.76 (s, 3H), 3.27-3.15 (m, 1H), 3.02-2.88 (m,1H), 2.42-2.21 (m, 2H), 2.21-2.01 (m, 2H), 2.01-1.85 (m, 2H), 1.81-1.68(m, 1H), 1.48-1.29 (m, 4H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):501 [M + H]⁺ 495

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52 (d, J = 8.8 Hz, 1H), 7.43-7.27 (m,5H), 4.80-4.67 (m, 1H), 4.60-4.49 (m, 1H), 4.35-4.26 (m, 1H), 4.09-3.91(m, 2H), 3.76 (s, 3H), 3.74-3.65 (m, 1H), 3.61-3.50 (m, 1H), 3.42-3.35(m, 1H), 3.29-3.23 (m, 1H), 3.20-3.07 (m, 1H), 2.95-2.83 (m, 1H),2.56-2.41 (m, 1H), 2.29-2.16 (m, 1H), 2.16-2.04 (m, 1H), 1.98-1.80 (m,2H), 1.78-1.65 (m, 1H), 1.11 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 512[M + H]⁺. 496

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46-7.41 (m, 2H), 7.30-7.26 (m, 2H),7.06-7.02 (m, 2H), 6.95-6.91 (m, 1H), 5.89-5.86 (m, 1H), 5.02-4.93 (m,1H), 4.80-4.76 (m, 1H), 3.79 (s, 3H), 3.29-3.23 (m, 1H), 2.94-2.90 (m,2H), 2.50-2.48 (m, 1H), 2.37-2.18 (m, 4H), 1.90-1.69 (m, 7H), 1.50 (m,1H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 492 [M + H]⁺. 497

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.52 (d, J = 9.0 Hz, 1H), 7.41 (d, J =9.3 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.1 Hz, 2H),4.86-4.74 (m, 1H), 4.28-4.23 (m, 2H), 4.06-3.93 (m, 3H), 3.79 (s, 3H),3.72-3.65 (m, 1H), 3.68-3.62 (m, 1H), 3.60-3.50 (m, 1H), 3.45-3.32 (m,1H), 2.99-2.92 (m, 1H), 2.32-2.21 (m, 5H), 1.78-1.72 (m, 3H), 1.23-1.12(m, 4H). LCMS (ES, m/z): 492 [M + H]⁺. 498

LCMS (ES, m/z): 511 [M + H]⁺ 499

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.49 (s, 1H), 7.99 (s, 1H), 7.65 (d, J= 8.8 Hz, 1H), 7.54-7.45 (m, 2H), 7.44-7.37 (m, 1H), 6.38 (s, 1H),5.05-4.93 (m, 1H), 4.83-4.71 (m, 1H), 3.79 (s, 3H), 3.30-3.14 (m, 1H),3.07-2.95 (m, 1H), 2.94-2.86 (m, 1H), 2.49-2.33 (m, 2H), 2.32-2.22 (m,1H), 2.15-2.03 (m, 1H), 2.02-1.90 (m, 1H), 1.83-1.68 (m, 1H), 1.65-1.44(m, 2H), 1.31-1.20 (m, 1H), 1.16 (d, J = 6.8 Hz, 3H), 0.97-0.86 (m, 1H).LCMS (ES, m/z): 519 [M + H]⁺. 500

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.47 (d, J = 9.0 Hz, 1H), 7.45-7.30 (m,2H), 7.27 (d, J = 8.3 Hz, 1H), 7.10-6.86 (m, 2H), 6.20 (s, 1H),5.00-4.88 (m, 1H), 4.81-4.65 (m, 1H), 4.57-4.47 (m, 2H), 3.76 (s, 3H),3.24-3.09 (m, 1H), 3.02-2.84 (m, 2H), 2.37-2.06 (m, 5H), 1.83-1.53 (m,3H), 1.52-1.40 (m, 1H), 1.40-1.22 (m, 1H), 1.13 (d, J = 6.6 Hz, 3H).LCMS (ES, m/z): 501 [M + H]⁺ 501

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52-7.33 (m, 6H), 6.22 (s, 1H),4.84-4.73 (m, 2H), 3.78 (s, 3H), 3.27-3.16 (m, 1H), 3.04-2.92 (m, 1H),2.90-2.88 (m, 1H), 2.46-2.35 (m, 2H), 2.30-2.22 (m, 1H), 2.15-2.02 (m,2H), 1.82-1.71 (m, 1H), 1.63-1.55 (m, 2H), 1.40-1.28 (m, 1H), 1.15 (d, J= 6.8 Hz, 3H), 1.14-1.01 (m, 1H). LCMS (ES, m/z): 512 [M + H]⁺. 502

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48 (d, J = 8.8 Hz, 1H), 7.40 (d, J =9.2 Hz, 1H), 7.23-7.18 (m, 2H), 7.05-7.02 (m, 1H), 4.78-4.65 (m, 2H),4.40-4.22 (m, 2H), 3.79 (s, 3H), 3.26-3.15 (m, 1H), 3.03-2.96 (m, 2H),2.38-2.12 (m, 5H), 1.79-1.62 (m, 3H), 1.41-1.23 (m, 2H), 1.16 (d, J =6.4 Hz, 3H). LCMS (ES, m/z): 498 [M + H]⁺. 503

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.50 (d, J = 9.2 Hz, 1H), 7.39 (d, J =8.8 Hz, 1H), 7.28-7.15 (m, 5H), 5.40-5-31 (m, 1H), 5.06-4.98 (m, 1H),4.80-4.76 (m, 1H), 3.82 (s, 3H), 3.56-3.40 (m, 1H), 3.29-3.24 (m, 1H),3.22-3.12 (m, 1H), 3.04-2.84 (m, 2H), 2.46-2.32 (m, 2H), 2.32-2.15 (m,3H), 1.80-1.65 (m, 3H), 1.53-1.38 (m, 2H), 1.13 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 492 [M + H]⁺ 504

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.82-7.53 (m, 2H), 7.51-7.36 (m, 1H),7.36-7.22 (m, 1H), 6.93-6.39 (m, 1H), 4.79-4.59 (m, 2H), 4.59-4.43 (m,1H), 4.40-4.09 (m, 1H), 4.05-3.85 (m, 1H), 3.76 (s, 3H), 3.26-3.10 (m,1H), 3.10-2.83 (m, 1H), 2.61-2.41 (m, 1H), 2.35-2.08 (m, 4H), 1.96-1.79(m, 1H), 1.79-1.53 (m, 3H), 1.49-1.36 (m, 4H), 1.32-1.22 (m, 1H), 1.13(d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 530 [M + H]⁺ 505

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.86-7.68 (m, 2H), 7.50-7.26 (m, 5H),5.07-4.94 (m, 2H), 4.88-4.80 (m, 1H), 4.56-4.47 (m, 1H), 4.29-4.20 (m,1H), 3.83 (s, 3H), 3.29-3.02 (m, 3H), 2.46-2.37 (m, 2H), 2.34-2.14 (m,3H), 1.96-1.84 (m, 1H), 1.83-1.66 (m, 2H), 1.23-1.07 (m, 5H). LCMS (ES,m/z): 492 [M + H]⁺. 506

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.52-7.38 (m, 3H), 7.32-7.28 (m, 3H),4.77-4.59 (m, 2H), 4.23-3.98 (m, 6H), 3.78-3.45 (m, 2H), 3.35-2.89 (m,4H), 2.52-2.48 (m, 1H), 2.25-2.16 (m, 2H), 1.90-1.43 (m, 3H), 1.14 (d, J= 6.6 Hz, 3H). LCMS (ES, m/z): 512 [M + H]⁺ 507

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49-7.38 (m, 3H), 7.37-7.30 (m, 1H),7.14 (d, J = 3.2 Hz, 1H), 7.11-7.03 (m, 1H), 6.38 (d, J = 3.2 Hz, 1H),4.83-4.69 (m, 1H), 4.47 (s, 2H), 4.41-4.27 (m, 1H), 3.78 (s, 6H),3.31-3.18 (m, 1H), 3.08-2.92 (m, 1H), 2.41-2.23 (m, 2H), 2.20-2.04 (m,2H), 2.02-1.88 (m, 2H), 1.84-1.69 (m, 1H), 1.50-1.32 (m, 4H), 1.17 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 515 [M + H]+. 508

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.43-7.37 (m, 3H), 7.27-7.17 (m, 2H),4.86-4.77 (m, 1H), 4.35-4.25 (m, 3H), 3.84 (s, 3H), 3.76 (s, 3H),3.25-2.85 (m, 2H), 2.69 (s, 1H), 2.45-2.03 (m, 6H), 1.78-1.71 (m, 1H),1.54-1.45 (m, 3H), 1.14 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 526 [M +H]⁺ 509

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56-7.48 (m, 1H), 7.44-7.37 (m, 1H),7.33-7.23 (m, 1H), 7.23-7.08 (m, 2H), 4.82-4.71 (m, 2H), 3.79 (s, 3H),3.32-3.10 (m, 4H), 3.09-2.85 (m, 3H), 2.41-2.17 (m, 5H), 1.91-1.82 (m,1H), 1.81-1.67 (m, 3H), 1.63-1.48 (m, 1H), 1.15 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 512 [M + H]⁺. 510

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.50 (d, J = 8.8 Hz, 1H), 7.43-7.32 (m,3H), 7.07-6.96 (m, 2H), 4.80-4.66 (m, 1H), 4.59-4.46 (m, 1H), 4.29-4.16(m, 1H), 4.04-3.91 (m, 2H), 3.76 (s, 3H), 3.72-3.61 (m, 1H), 3.61-3.47(m, 1H), 3.31-3.22 (m, 2H), 3.20-3.07 (m, 1H), 2.95-2.83 (m, 1H),2.54-2.37 (m, 1H), 2.27-2.17 (m, 1H), 2.15-2.02 (m, 1H), 2.00-1.78 (m,2H), 1.78-1.63 (m, 1H), 1.10 (d, J = 6.7, 2.0 Hz, 3H). LCMS (ES, m/z):496 [M + H]⁺. 511

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.44 (d, J = 8.8 Hz, 1H), 7.33 (d, J =8.8 Hz, 1H), 7.18-6.98 (m, 3H), 5.05-4.90 (m, 1H), 4.85-4.72 (m, 1H),4.28-4.21 (m, 1H), 3.77 (s, 3H), 3.73-3.65 (m, 1H), 3.42-3.33 (m, 1H),3.18-3.10 (m, 1H), 2.92-2.85 (m, 1H), 2.31-2.12 (m, 6H), 2.11-1.92 (m,3H), 1.90-1.67 (m, 4H), 1.12 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 491[M + H]⁺. 512

¹H-NMR (d6-DMSO, 400 MHz) δ (ppm): 7.90-7.84 (m, 1H), 7.69-7.62 (m, 1H),7.00 (s, 2H), 6.93 (s, 1H), 4.91-4.81 (m, 1H), 4.78-4.68 (m, 1H),4.68-4.60 (m, 1H), 4.39-4.31 (m, 1H), 3.77 (s, 3H), 3.71 (s, 3H),3.05-2.93 (m, 3H), 2.36-2.24 (m, 1H), 2.24-2.05 (m, 3H), 2.04-1.96 (m,1H), 1.86-1.65 (m, 3H), 1.40-1.33 (m, 1H), 1.27-1.13 (m, 1H), 1.09 (d, J= 6.4 Hz, 3H). LCMS (ES, m/z): 526 [M + H]⁺. 513

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52-7.30 (m, 7H), 5.84 (s, 1H),4.80-4.72 (m, 2H), 3.79 (s, 3H), 3.55 (s, 3H), 3.32-3.21 (m, 1H),3.08-2.90 (m, 2H), 2.64-2.35 (m, 3H), 2.13-2.05 (m, 1H), 1.98-1.73 (m,2H), 1.61-1.45 (m, 2H), 1.35-1.21 (m, 1H), 1.17 (d, J = 6.8 Hz, 3H),0.85-0.77 (m, 1H),. LCMS (ES, m/z): 492 [M + H]⁺. 514

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55 (d, J = 8.8 Hz, 1H), 7.38 (d, J =9.2 Hz, 1H), 4.83-4.65 (m, 2H), 3.79 (s, 3H), 3.23-3.09 (m, 1H),3.09-2.95 (m, 3H), 2.95-2.79 (m, 1H), 2.51-2.33 (m, 2H), 2.33-2.15 (m,3H), 1.99-1.82 (m, 6H), 1.82-1.49 (m, 8H), 1.29-1.25 (m, 2H), 1.13 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 468 [M + H]⁺. 515

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.62 (d, J = 9.2 Hz, 1H), 7.53 (d, J =8.8 Hz, 1H), 7.41 (d, J = 9.2 Hz, 1) 7.20-7.13 (m, 2H), 6.67-6.30 (m,2H), 4.98-4.95 (m, 1H), 4.76-4.71 (m, 1H), 3.78 (s, 3H), 3.15-2.86 (m,3H), 2.46-2.20 (m, 5H), 1.81-1.53 (m, 5H), 1.13 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 562 [M + H]⁺. 516

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47 (t, J = 8.0 Hz, 1H), 7.35 (d, J =8.8 Hz, 1H), 7.28-7.16 (m, 3H), 7.16-7.03 (m, 3H), 6.91-6.59 (m, 3H),4.81-4.68 (m, 1H), 4.35-4.24 (m, 1H), 3.84 (s, 3H), 3.75 (s, 3H),3.59-3.48 (m, 1H), 3.29-3.13 (m, 2H), 3.07-2.91 (m, 1H), 2.33-2.21 (m,1H), 1.79-1.66 (m, 1H), 1.13 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 500[M + H]⁺. 517

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.81-7.75 (m, 2H), 7.27-7.26 (m, 3H),7.19-7.15 (m, 2H), 5.72-5.66 (m, 1H), 4.84-4.83 (m, 1H), 4.42-4.37 (m,1H), 3.82 (s, 3H), 3.62-3.60 (m, 1H), 3.33-3.27 (m, 1H), 3.12-3.09 (m,2H), 2.52-2.49 (m, 1H), 2.26-2.02 (m, 4H), 2.00 (s, 3H), 1.95-1.88 (m,3H), 1.69-1.65 (m, 1H), 1.45-1.37 (m, 1H), 1.16 (d, J = 6.4 Hz, 3H),0.38-0.36 (m, 1H). LCMS (ES, m/z): 533 [M + H]⁺. 518

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.72 (d, J = 8.0 Hz, 1H), 7.63 (d, J =9.2 Hz, 1H), 7.41-7.39 (d, J = 9.2 Hz, 1H), 6.90 (d, J = 7.6 Hz, 1H),4.72-4.74 (m, 1H), 4.50-4.39 (m, 3H), 3.95 (s, 3H), 3.79 (s, 3H),3.26-3.15 (m, 1H), 3.03-2.96 (m, 1H), 2.49-2.40 (m, 1H), 2.38-2.25 (m,3H), 2.15-2.07 (m, 2H), 1.80-1.36 (m, 3H), 1.61-1.45 (m, 2H), 1.16 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 527, 529 [M + H]⁺. 519

LCMS (ES, m/z): 496 [M + H]⁺. 520

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53 (s, 1H), 7.46 (s, 1H), 7.42-7.34(m, 2H), 5.18-5.00 (m, 1H), 4.83-4.70 (m, 1H), 4.70-4.57 (m, 1H),4.57-4.43 (m, 1H), 4.03-3.86 (m, 1H), 3.79 (s, 3H), 3.43-3.35 (m, 2H),3.26-3.11 (m, 3H), 3.04-2.88 (m, 1H), 2.37-2.18 (m, 2H), 2.18-2.01 (m,1H), 1.82-1.64 (m, 1H), 1.44 (d, J = 6.9 Hz, 3H), 1.15 (d, J = 6.6 Hz,3H). LCMS (ES, m/z): 457 [M + H]⁺. 521

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.87-7.81 (m, 1H), 7.55-7.48 (m, 1H),7.47-7.40 (m, 1H), 7.40-7.32 (m, 1H), 7.32-7.21 (m, 2H), 4.82-4.73 (m,1H), 4.57-4.46 (m, 1H), 3.79 (s, 3H), 3.49-3.38 (m, 4H), 3.23-3.10 (m,1H), 3.00-2.88 (m, 1H), 2.32-2.14 (m, 3H), 1.96-1.88 (m, 2H), 1.84-1.71(m, 3H), 1.70-1.55 (m, 3H), 1.46-1.36 (m, 1H), 1.14 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 476 [M + H]⁺. 522

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48 (d, J = 9.2 Hz, 1H), 7.40 (d, J =8.8 Hz, 1H), 7.25-7.21 (m, 2H), 7.15-7.12 (m, 2H), 6.97-6.93 (m, 1H),6.07-6.05 (m, 1H), 5.15-5.02 (m, 1H), 4.77-4.74 (m, 1H), 3.77 (s, 3H),3.18-3.15 (m, 1H), 3.03-2.92 (m, 1H), 2.47-2.36 (m, 1H), 2.26-2.20 (m,4H), 1.93 (d, J = 6.8 Hz, 3H), 1.85-1.81 (m, 1H), 1.76-1.60 (m, 5H),1.12 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 504 [M + H]⁺. 523

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51-7.30 (m, 6H), 6.24 (s, 1H),4.93-4.74 (m, 2H), 3.78 (s, 3H), 3.33-3.17 (m, 1H), 3.01-2.94 (m, 1H),2.82 (m, 1H), 2.37-2.35 (m, 2H), 2.29-2.24 (m, 2H), 2.08-2.05 (m, 1H),1.77-1.72 (m, 1H), 1.60-1.54 (m, 2H), 1.34-1.30 (m, 1H), 1.15 (d, J =6.8 Hz, 3H), 1.14-1.05 (m, 1H). LCMS (ES, m/z): 512 [M + H]⁺. 524

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.59-7.45 (m, 5H), 7.39 (d, J = 8.8 Hz,1H), 6.92-6.56 (m, 1H), 4.82-4.68 (m, 1H), 4.48-4.29 (m, 2H), 4.10-3.89(m, 3H), 3.83-3.68 (m, 4H), 3.62-3.47 (m, 1H), 3.45-3.34 (m, 1H),3.21-3.06 (m, 1H), 3.00-2.86 (m, 1H), 2.45-2.31 (m, 1H), 2.30-2.15 (m,1H), 1.83-1.62 (m, 3H), 1.28-1.17 (m, 1H), 1.13 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 528 [M + H]⁺. 525

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48-7.46 (m, 1H), 7.42-7.39 (m, 6H),6.56 (s, 1H), 4.81-4.79 (m, 1H), 4.75-4.60 (m, 1H), 3.79 (s, 3H),3.31-3.29 (m, 1H), 3.03-2.93 (m, 2H), 2.40-2.31 (m, 3H), 2.15-2.01 (m,5H), 1.82-1.74 (m, 1H), 1.65-1.60 (m, 2H), 1.18-1.08 (m, 4H), 1.02-0.91(m, 1H). LCMS (ES, m/z): 519 [M + H]⁺. 526

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.51-7.37 (m, 2H), 7.17 (d, J = 2.1 Hz,1H), 5.88 (s, 1H), 4.81-4.68 (m, 1H), 4.57-4.34 (m, 2H), 4.34-4.18 (m,1H), 4.05-3.88 (m, 1H), 3.76 (s, 3H), 3.24-3.11 (m, 1H), 3.01-2.85 (m,1H), 2.62-2.38 (m, 1H), 2.38-2.08 (m, 8H), 1.95-1.79 (m, 1H), 1.79-1.55(m, 3H), 1.55-1.40 (m, 3H), 1.35-1.27 (m, 1H), 1.12 (d, J = 6.6 Hz, 3H).LCMS (ES, m/z): 494 [M + H]⁺ 527

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47 (d, J = 9.2 Hz, 1H), 7.36 (d, J =9.2 Hz, 1H), 7.25-7.23 (m, 4H), 7.21-7.13 (m, 1H), 4.81-4.57 (m, 2H),3.77 (s, 3H), 3.33-3.12 (m, 4H), 3.06-2.81 (m, 3H), 2.41-2.14 (m, 5H),1.83-1.65 (m, 3H), 1.52-1.39 (m, 2H), 1.12 (d, J = 6.8 Hz, 3H). LCMS(ES, m/z): 476 [M + H]⁺. 528

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.57-7.40 (m, 4H), 7.30-7.28 (m, 3H),6.12 (s, 1H), 4.95-4.90 (m, 1H), 4.84-4.79 (m, 1H), 3.79 (s, 3H),3.33-3.25 (m, 1H), 3.03-2.82 (m, 2H), 2.49-2.30 (m, 2H), 2.29-2.21 (m,1H), 2.12-2.07 (m, 1H), 1.99-1.90 (m, 1H), 1.85-1.79 (m, 1H), 1.64-1.49(m, 2H), 1.40-1.29 (m, 1H), 1.16 (d, J = 6.4 Hz, 3H), 0.95-0.89 (m, 1H).LCMS (ES, m/z): 478 [M + H]⁺. 529

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.55-7.40 (m, 2H), 7.30-7.26 (m, 2H),7.05 (d, J = 7.5 Hz, 2H), 7.00-6.95 (m, 1H), 5.91-5.88 (m, 1H),4.85-4.77 (m, 2H), 3.78 (s, 3H), 3.27-3.14 (m, 1H), 2.97-2.90 (m, 1H),2.55-2.30 (m, 2H), 2.30-2.17 (m, 3H), 2.17-2.08 (m, 1H), 2.04-1.91 (m,1H), 1.87-1.80 (m, 3H), 1.76-170 (m, 1H), 1.62-1.40 (m, 3H), 1.13 (d, J= 6.9 Hz, 1H). LCMS (ES, m/z): 492 [M + H]⁺. 530

8.30 (s, 1H), 7.69 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.47 (d, J = 9.2Hz, 1H), 4.84-4.74 (m, 2H), 3.79 (s, 3H), 3.23-3.15 (m, 1H), 3.03-2.86(m, 2H), 2.56-2.42 (m, 1H), 2.52-2.05 (m, 6H), 1.79-1.63 (m, 7H),1.35-1.24 (m, 1H), 1.16 (d, J = 6.4 Hz, 3H), 1.07-1.05 (m, 4H). LCMS(ES, m/z): 530 [M + H]⁺. 531

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.57-7.55 (m, 1H), 7.44-7.42 (m, 1H),5.14-5.04 (m, 2H), 4.79-4.75 (m, 1H), 3.78 (s, 3H), 3.44-3.40 (m, 1H),3.24-3.20 (m, 1H), 2.95-2.88 (m, 2H), 2.54-2.48 (m, 1H), 2.38-2.25 (m,4H), 1.95-1.87 (m, 4H), 1.87-1.73 (m, 5H), 1.69-1.67 (m, 3H), 1.55-1.51(m, 1H), 1.41-1.19 (m, 5H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z):498 [M + H]⁺. 532

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.50-7.35 (m, 2H), 7.05-6.71 (m, 2H),4.78-4.74 (m, 1H), 4.37 (s, 2H), 4.27-4.19 (m, 1H), 3.94 (s, 3H), 3.79(s, 3H), 3.22-3.16 (m, 1H), 2.98-2.90 (m, 1H), 2.59-2.46 (m, 1H),2.36-2.19 (m, 3H), 2.12-1.92 (m, 2H), 1.85-1.69 (m, 1H), 1.55-1.44 (m,4H), 1.16 (d, J = 6.9 Hz, 3H). LCMS (ES, m/z): 528 [M + H]⁺. 533

¹H-NMR (d6-DMSO, 400 MHz) δ (ppm): 12.60 (br, 1H), 7.91-7.84 (m, 1H),7.69-7.62 (m, 1H), 7.43-7.38 (m, 2H), 7.32-7.05 (m, 3H), 4.85-4.65 (m,3H), 4.43-4.36 (m, 1H), 3.71 (s, 3H), 3.07-2.91 (m, 3H), 2.35-2.25 (m,1H), 2.22-2.08 (m, 3H), 2.04-1.96 (m, 1H), 1.82-1.66 (m, 3H), 1.49-1.41(m, 1H), 1.29-1.21 (m, 1H), 1.09 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z):528 [M + H]⁺. 534

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.84-7.80 (m, 2H), 7.58-7.56 (m, 2H),7.48-7.43 (m, 3H), 4.86-4.82 (m, 1H), 4.69-4.65 (m, 1H), 3.82 (s, 3H),3.26-3.08 (m, 3H), 3.03-2.98 (m, 1H), 2.65-2.45 (m, 2H), 2.52-1.82 (m,5H), 1.69-1.62 (m, 1H), 1.52-1.48 (m, 1H), 1.20 (d, J = 6.4 Hz, 3H),1.01 (t, J = 7.2 Hz, 3H), 0.88-0.79 (m, 2H). LCMS (ES, m/z): 506 [M +H]⁺. 535

LCMS (ES, m/z): 507 [M + H]⁺. 536

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.30 (d, J = 8.7 Hz, 1H), 7.21-7.06 (m,9H), 6.77 (d, J = 8.7 Hz, 1H), 4.86-4.71 (m, 1H), 4.30-4.20 (m, 1H),3.89 (s, 3H), 3.75 (s, 3H), 3.55-3.42 (m, 1H), 3.32-2.82 (m, 3H),2.32-2.21 (m, 1H), 1.75-1.58 (m, 1H), 1.12 (d, J = 6.6 Hz, 3H). LCMS(ES, m/z): 500 [M + H]⁺. 537

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.63 (d, J = 8.8 Hz, 1H), 7.55 (d, J =9.2 Hz, 1H), 7.21-7.19 (m, 1H), 7.08-7.04 (m, 1H), 6.46 (s, 1H),4.94-4.92 (m, 1H), 4.80-4.78 (m, 1H), 3.79 (s, 3H), 3.78 (s, 3H),3.27-3.21 (m, 1H), 3.05-2.89 (m, 2H), 2.51-2.41 (m, 1H), 2.38-2.15 (m,4H), 1.80-1.69 (m, 3H), 1.52-1.43 (m, 2H), 1.15 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 544 [M + H]⁺. 538

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47-7.24 (m, 3H), 7.04-6.86 (m, 3H),6.21 (s, 1H), 4.87-4.73 (m, 1H), 3.77 (s, 6H), 3.33-3.32 (m, 1H),3.00-2.77 (m, 2H), 2.29-2.05 (m, 5H), 1.75-1.31 (m, 5H), 1.79-1.45 (m,4H). LCMS (ES, m/z): 508 [M + H]⁺. 539

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.47 (d, J = 9.0 Hz, 1H), 7.34 (d, J =9.0 Hz, 1H), 7.20 (d, J = 8.1 Hz, 2H), 7.08 (d, J = 7.8 Hz, 2H),4.84-4.70 (m, 1H), 4.44-4.42 (m, 1H), 4.17-4.12 (m, 1H), 3.95-3.88 (m,2H), 3.76 (s, 3H), 3.67-3.52 (m, 2H), 3.34-3.08 (m, 3H), 2.93-2.87 (m,1H), 2.44-2.08 (m, 6H), 1.95-1.65 (m, 3H), 1.10 (d, J = 6.6 Hz, 3H).LCMS (ES, m/z): 492 [M + H]⁺ 540

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.11-8.09 (m, 1H), 7.84 (s, 2H),7.81-7.73 (m, 1H), 7.09-7.02 (m, 1H), 7.02-6.95 (m, 1H), 5.28-5.13 (m,1H), 3.83 (m, 3H), 3.40-3.30 (m, 1H), 3.25-3.10 (m, 1H), 3.10-2.99 (m,1H), 2.70-2.56 (m, 1H), 2.54-2.36 (m, 2H), 2.36-2.20 (m, 3H), 2.09-1.83(m, 5H), 1.83-1.67 (m, 4H), 1.22-1.10 (d, J = 6.4 Hz, 3H). LCMS (ES,m/z): 505 [M + H]⁺. 541

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49 (d, J = 8.8 Hz, 1H), 7.40 (d, J =8.8 Hz, 1H), 6.70-6.68 (m, 1H), 6.67-6.51 (m, 2H), 4.82-4.72 (m, 1H),4.50-4.31 (m, 2H), 3.76 (s, 3H), 3.74 (s, 3H), 3.28-3.12 (m, 1H),3.04-2.92 (m, 1H), 2.78-2.76 (m, 1H), 2.40-2.21 (m, 4H), 2.21-2.02 (m,1H), 1.83-1.69 (m, 1H), 1.69-1.50 (m, 2H), 1.48-1.20 (m, 3H), 1.15 (d, J= 6.4 Hz, 3H). LCMS (ES, m/z): 510 [M + H]⁺. 542

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48-7.45 (m, 1H), 7.44-7.29 (m, 5H),7.28-7.21 (m, 1H), 4.81-4.66 (m, 2H), 3.78 (s, 3H), 3.41-3.33 (m, 1H),3.05-2.92 (m, 1H), 2.78-2.71 (m, 1H), 2.43-2.22 (m, 2H), 2.11 (s, 3H),2.10-1.95 (m, 2H), 1.79-1.71 (m, 2H), 1.65-1.30 (m, 4H), 1.17 (d, J =6.4 Hz, 3H). LCMS (ES, m/z): 492 [M + H]⁺. 543

¹H NMR (CD₃OD, 300 MHz) δ (ppm): 7.88-7.81 (m, 2H), 7.22 (d, J = 8.7 Hz,2H), 6.89 (d, J = 8.7 Hz, 2H), 4.89-4.87 (m, 1H), 4.62-4.54 (m, 3H),3.82 (s, 3H), 3.09-3.00 (m, 2H), 2.98 (s, 6H), 2.54-2.50 (m, 1H),2.35-2.21 (m, 3H), 2.17-2.13 (m, 2H), 1.98-1.92 (m, 1H), 1.64-1.52 (m,4H), 1.19 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 505 [M + H]⁺. 544

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53-7.36 (m, 2H), 7.31 (d, J = 8.4 Hz,2H), 7.12 (d, J = 8.4 Hz, 2H), 7.03-6.51 (m, 1H), 4.81-4.67 (m, 1H),4.41 (s, 2H), 4.31-4.15 (m, 1H), 3.78 (s, 3H), 3.27-3.10 (m, 1H),3.03-2.87 (m, 1H), 2.47-2.32 (m, 1H), 2.32-2.15 (m, 3H), 2.15-1.97 (m,2H), 1.84-1.66 (m, 1H), 1.64-1.37 (m, 4H), 1.16 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 528 [M + H]⁺ 545

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.62-7.42 (m, 4H), 7.34-7.01 (m, 3H),5.22 (d, J = 7.2 Hz, 1H), 4.88-4.70 (m, 2H), 3.78 (s, 3H), 3.70-3.51 (m,1H), 3.23-3.15 (m, 1H), 3.01-2.94 (m, 2H), 2.45-2.15 (m, 4H), 1.92-1.51(m, 6H), 1.47 (d, J = 6.8 Hz, 3H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES,m/z): 506 [M + H]⁺ 546

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.56-7.47 (m, 3H), 6.81 (d, J = 7.5 Hz,1H), 6.61 (d, J = 8.4 Hz, 1H), 4.78-4.72 (m, 3H), 4.44 (s, 1H), 3.81 (3,3H), 3.76 (s, 3H), 3.25-3.15 (m, 1H), 2.99-2.85 (m, 2H), 2.45-2.15 (m,5H), 1.80-1.55 (m, 3H), 1.35-1.25 (m, 2H), 1.13 (d, J = 6.6 Hz, 3H).LCMS (ES, m/z): 493 [M + H]⁺. 547

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52 (d, J = 9.2 Hz, 1H), 7.38 (d, J =9.2 Hz, 1H), 4.78-4.74 (m, 2H), 3.79 (s, 3H), 3.16-3.14 (m, 1H),3.03-2.92 (m, 4H), 2.45-2.42 (m, 2H), 2.29-2.24 (m, 2H), 1.94-1.89 (m,4H), 1.77-1.59 (m, 8H), 1.40-1.25 (m, 5H), 1.14 (d, J = 6.4 Hz, 3H),1.08-1.02 (m, 2H). LCMS (ES, m/z): 482 [M + H]⁺. 548

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.62-7.50 (m, 2H), 7.42-7.24 (m, 5H),5.21-5.13 (m, 1H), 4.83-4.70 (m, 2H), 3.80 (s, 3H), 3.51 (d, J = 7.2 Hz,2H), 3.17-3.05 (m, 1H), 3.02-2.89 (m, 2H), 2.31-2.14 (m, 5H), 1.86-1.67(m, 3H), 1.51-1.40 (m, 1H), 1.32-1.24 (m, 1H), 1.14 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 492 [M + H]⁺. 549

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.45-7.35 (m, 2H), 7.12-7.08 (m, 4H),4.86-4.60 (m, 2H), 4.39-4.23 (m, 2H), 3.76 (s, 3H), 3.30-3.10 (m, 1H),2.99-2.86 (m, 2H), 2.40-2.00 (m, 8H), 1.80-1.52 (m, 3H), 1.35-1.12 (m,5H) LCMS (ES, m/z): 476 [M + H]⁺. 550

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48 (d, J = 8.8 Hz, 1H), 7.37 (d, J =8.8 Hz, 1H), 7.05-7.13 (m, 1H), 7.00-6.90 (m, 2H), 4.62-4.77 (m, 2H),3.77 (s, 3H), 3.27-3.09 (m, 4H), 3.04-2.84 (m, 3H), 2.38-2.17 (m, 8H),1.83-1.62 (m, 3H), 1.61-1.43 (m, 2H), 1.12 (d, J = 6.8 Hz, 3H). LCMS(ES, m/z): 508 [M + H]⁺. 551

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.94-7.79 (m, 3H), 7.40 (s, 1H),4.75-4.61 (m, 2H), 4.61-4.43 (m, 1H), 4.43-4.28 (m, 1H), 3.83 (s, 3H),3.19-3.01 (m, 2H), 2.69-2.54 (m, 1H), 2.46-2.17 (m, 5H), 2.12-1.99 (m,1H), 1.99-1.86 (m, 1H), 1.86-1.71 (m, 1H), 1.71-1.51 (m, 5H), 1.38-1.24(m, 1H), 1.18 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 514 [M + H]⁺. 552

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.54 (s, 1H), 8.45 (s, 1H), 8.38 (d, J= 2.4 Hz, 1H), 7.45 (d, J = 8.8 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H),4.84-4.74 (m, 1H), 4.50-4.35 (m, 1H), 4.01-3.85 (m, 1H), 3.79 (s, 3H),3.60-3.45 (m, 1H), 3.25-3.11 (m, 2H), 2.96-2.81 (m, 1H), 2.60-2.49 (m,1H), 2.46-2.11 (m, 5H), 2.01-1.85 (m, 1H), 1.79-1.61 (m, 3H), 1.61-1.51(m, 1H), 1.50 (d, J = 6.8 Hz, 3H), 1.13 (d, J = 6.8 Hz, 3H). LCMS (ES,m/z): 492 [M + H]⁺. 553

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48 (d, J = 8.8 Hz, 1H), 7.40 (d, J =9.2 Hz, 1H), 6.92-6.76 (m, 2H), 4.78-4.67 (m, 1H), 4.37 (s, 2H),4.29-4.15 (m, 1H), 3.86 (s, 3H), 3.76 (s, 3H), 3.21-3.10 (m, 1H),2.98-2.80 (m, 1H), 2.53-2.38 (m, 1H), 2.38-2.19 (m, 3H), 2.19-2.04 (m,2H), 1.78-1.59 (m, 3H), 1.59-1.38 (m, 2H), 1.13 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 528 [M + H]⁺ 554

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47-7.01 (m, 7H), 5.65-5.50 (m, 1H),4.84-4.74 (m, 1H), 4.51-4.35 (m, 1H), 3.79 (s, 3H), 3.50-3.15 (m, 3H),3.03-2.82 (m, 2H), 2.41-2.22 (m, 2H), 2.20-1.95 (m, 6H), 1.81-1.70 (m,1H), 1.69-1.55 (m, 2H), 1.35-1.20 (m, 1H), 1.16 (d, J = 6.8 Hz, 3H),0.70-0.60 (m, 1H). LCMS (ES, m/z): 533 [M + H]⁺. 555

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.02 (d, J = 7.6 Hz, 1H), 7.54-7.36 (m,4H), 7.12 (d, J = 7.6 Hz, 1H) 4.88-4.76 (m, 3H), 4.39-4.33 (m, 1H), 3.78(s, 3H), 3.21-2.84 (m, 2H), 2.28-2.13 (m, 3H), 1.83-1.56 (m, 6H),1.39-1.21 (m, 3H), 1.16 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 462 [M +H]⁺ 556

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.34 (s, 1H), 7.53-7.50 (m, 1H),7.31-7.28 (m, 1H), 4.78-4.58 (m, 2H), 4.50-4.32 (m, 2H), 3.69 (s, 3H),3.05-2.96 (m, 1H), 2.87-2.75 (m, 6H), 2.31-2.10 (m, 3H), 2.09-2.03 (m,2H), 1.75-1.58 (m, 4H), 1.749-1.70 (m, 4H), 1.45-1.30 (m, 1H), 1.11 (d,J = 6.8 Hz, 3H). LCMS (ES, m/z): 518 [M + H]⁺. 557

¹H NMR (400 MHz, CD₃OD) δ (ppm): 7.57 (d, J = 8.8 Hz, 1H), 7.43 (d, J =9.2 Hz, 1H), 5.28-5.16 (m, 2H), 4.77-4.76 (m, 1H), 3.94-3.92 (m, 1H),3.87-3.84 (m, 1H), 3.79 (s, 3H), 3.60-3.58 (m, 1H), 3.46-3.37 (m, 2H),3.16-3.14 (m, 1H), 3.02-3.00 (m, 1H), 2.95-2.90 (m, 1H), 2.55-2.53 (m,1H), 2.39-2.36 (m, 2H), 2.30-2.24 (m, 2H), 2.09-2.06 (m, 1H), 1.92-1.90(m, 2H), 1.78-1.52 (m, 9H), 1.14 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z):500 [M + H]⁺ 558

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58-7.56 (m, 1H), 7.43-7.41 (m, 1H),5.19-5.16 (m, 1H), 5.05-5.00 (m, 1H), 4.78-4.76 (m, 1H), 3.79 (s, 3H),3.42-3.38 (m, 1H), 3.21-3.05 (m, 1H), 2.93-2.89 (m, 1H), 2.64-2.54 (m,1H), 2.53-2.37 (m, 2H), 2.29-2.25 (m, 3H), 2.15-2.90 (m, 3H), 1.75-1.60(m, 5H), 1.65 (d, J = 8.0 Hz, 3H), 1.57-1.51 (m, 1H), 1.42-1.35 (m, 2H),1.36-1.21 (m, 4H), 1.14 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 498 [M +H]⁺. 559

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58 (d, J = 9.2 Hz, 1H), 7.40 (d, J =9.2 Hz, 1H), 4.89-4.81 (m, 1H), 4.85-4.81 (m, 1H), 3.96-3.89 (m, 1H),3.88-3.80 (m, 1H), 3.79 (s, 3H), 3.48 (m, 1H), 3.17 (m, 3H), 3.01-2.92(m, 2H), 2.52-2.32 (m, 2H), 2.32-2.18 (m, 3H), 1.99-1.87 (m, 3H),1.79-1.69 (m, 2H), 1.69-1.62 (m, 2H), 1.59-1.45 (m, 3H), 1.40-1.29 (m,1H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 470 [M + H]⁺. 560

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47-7.29 (m, 2H), 7.19-7.06 (m, 1H),7.07-6.94 (m, 2H), 4.81-4.67 (m, 1H), 4.03-3.92 (m, 1H), 3.88 (s, 3H),3.78 (s, 3H), 3.33-3.25 (m, 1H), 3.01-2.89 (m, 1H), 2.41-2.26 (m, 2H),2.26-2.12 (m, 2H), 2.06-1.92 (m, 2H), 1.84 (s, 6H), 1.76-1.62 (m, 1H),1.51-1.41 (m, 2H), 1.26-1.03 (m, 5H). LCMS (ES, m/z): 538 [M + H]⁺. 561

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49-7.40 (m, 2H), 7.10-6.95 (m, 2H),6.80-6.70 (m, 1H), 4.80-4.70 (m, 1H), 4.35 (s, 2H), 4.30-4.15 (m, 1H),3.95 (s, 3H), 3.75 (s, 3H), 3.25-2.85 (m, 2H), 2.45-2.05 (m, 6H),1.80-1.30 (m, 5H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 510 [M +H]⁺. 562

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.26 (s, 1H), 7.88 (s, 2H), 7.80-7.72(m, 1H), 7.01-6.95 (m, 1H), 5.14-5.03 (m, 1H), 4.90-4.83 (m, 1H),4.72-4.55 (m, 2H), 4.20-4.11 (m, 1H), 3.83 (s, 3H), 3.17-2.99 (m, 3H),2.50-2.39 (m, 1H), 2.37-2.17 (m, 4H), 1.99-1.88 (m, 1H), 1.88-1.75 (m,2H), 1.68-1.60 (m, 1H), 1.50-1.35 (m, 1H), 1.18 (d, J = 6.8 Hz, 3H),0.87-0.79 (m, 2H), 0.79-0.67 (m, 2H). LCMS (ES, m/z): 519 [M + H]⁺. 563

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55-7.34 (m, 2H), 7.25-7.07 (m, 4H),4.83-4.62 (m, 2H), 4.32-4.21 (m, 1H), 4.18-4.07 (m, 1H), 4.06-3.90 (m,2H), 3.88-3.70 (m, 4H), 3.70-3.54 (m, 1H), 3.26-3.10 (m, 2H), 3.02-2.89(m, 1H), 2.81-2.61 (m, 1H), 2.36-2.18 (m, 4H), 1.80-1.71 (m, 1H),1.67-1.55 (m, 1H), 1.13 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 528 [M +H]⁺. 564

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.89-7.83 (m, 2H), 7.77-7.72 (m, 1H),7.53-7.50 (m, 1H), 7.34-7.31 (m, 1H), 7.21-6.93 (m, 1H), 6.74-6.72 (m,1H), 4.95-4.93 (m, 1H), 4.85-4.81 (m, 2H), 3.83 (s, 3H), 3.19-3.12 (m,1H), 3.02-2.95 (m, 2H), 2.50-2.48 (m, 1H), 2.30-2.16 (m, 4H), 1.89-1.73(m, 4H), 1.50-1.42 (m, 1H), 1.16 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z):546 [M + H]⁺. 565

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.82 (s, 1H), 7.52 (d, J = 8.4 Hz, 1H),7.48-7.40 (m, 3H), 6.35 (s, 1H), 4.96-4.89 (m, 1H), 4.79-4.75 (m, 1H),3.78 (s, 3H), 3.30-3.24 (m, 1H), 3.22-3.01 (m, 1H), 3.00-2.91 (m, 1H),2.64 (s, 3H), 2.43-2.42 (m, 2H), 2.40-2.25 (m, 1H), 2.09-2.00 (m, 1H),1.99-1.96 (m, 1H), 1.78-1.73 (m, 1H), 1.56-1.47 (m, 2H), 1.32-1.26 (m,1H), 1.15 (d, J = 6.4 Hz, 3H), 0.95-0.92 (m, 1H). LCMS (ES, m/z): 533[M + H]⁺. 566

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.72 (s, 1H), 8.02-7.95 (m, 2H),7.55-7.45 (m, 1H), 7.45-7.38 (m, 1H), 6.99 (s, 1H), 6.38 (s, 1H),5.06-4.96 (m, 1H), 4.81-4.72 (m, 1H), 3.78 (s, 3H), 3.30-3.18 (m, 1H),2.99-2.87 (m, 1H), 2.84-2.80 (m, 1H), 2.43-2.31 (m, 1H), 2.29-2.20 (m,2H), 2.18-2.11 (m, 1H), 2.08-2.00 (m, 1H), 1.83-1.67 (m, 3H), 1.67-1.50(m, 2H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 519 [M + H]⁺. 567

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.38-7.21 (m, 2H), 7.18-7.04 (m, 3H),7.04-6.96 (m, 2H), 4.78-4.65 (m, 1H), 4.38-4.33 (m, 1H), 3.77 (s, 3H),3.63-3.51 (m, 1H), 3.29-3.19 (m, 1H), 3.19-2.89 (m, 6H), 2.90-2.74 (m,1H), 2.35-2.16 (m, 3H), 1.98-1.92 (m, 1H), 1.77-1.56 (m, 2H), 1.54 (d, J= 6.8 Hz, 3H), 1.41-1.34 (m, 1H), 1.12 (d, J = 6.8 Hz, 3H), 0.77-0.69(m, 1H). LCMS (ES, m/z): 461 [M + H]⁺. 568

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.43 (d, J = 9.2 Hz, 1H), 7.36 (d, J =8.8 Hz, 1H), 7.16 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 9.2 Hz, 2H),4.81-4.63 (m, 2H), 4.40-4.19 (m, 2H), 3.82-3.70 (m, 6H), 3.26-3.12 (m,1H), 3.02-2.85 (m, 2H), 2.37-1.98 (m, 5H), 1.80-1.69 (m, 1H), 1.68-1.55(m, 2H), 1.37-1.09 (m, 5H). LCMS (ES, m/z): 492 [M + H]⁺. 569

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.47 (d, J = 9.2 Hz, 1H), 7.38 (d, J =8.8 Hz, 1H), 7.26-7.17 (m, 5H), 5.29 (t, J = 7.2 Hz, 1H), 4.78-4.76 (m,1H), 4.60-4.55 (m, 1H), 3.78 (s, 3H), 3.34-3.32 (m, 2H), 3.20-3.17 (m,1H), 2.96-2.92 (m, 1H), 2.51-2.46 (m, 1H), 2.30-2.19 (m, 4H), 2.16-2.05(m, 1H), 1.97-1.95 (m, 1H), 1.72-1.32 (m, 4H), 1.13 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 492 [M + H]⁺. 570

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52 (d, J = 9.2 Hz, 1H), 7.39 (d, J =9.2 Hz, 1H), 4.81-4.68 (m, 2H), 3.78 (s, 3H), 3.20-3.16 (m, 1H),3.09-2.98 (m, 1H), 2.90-2.84 (m, 3H), 2.42-2.34 (m, 3H), 2.32-2.18 (m,3H), 2.14-2.05 (m, 2H), 1.93-1.82 (m, 6H), 1.82-1.58 (m, 5H), 1.17-1.10(d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 454 [M + H]⁺. 571

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55-7.21 (m, 7H), 4.81-4.63 (m, 1H),4.59-4.41 (m, 1H), 4.41-4.21 (m, 1H), 4.22-4.04 (m, 1H), 3.78 (s, 2H),3.22-3.09 (m, 1H), 3.04-2.92 (m, 1H), 2.92-2.74 (m, 3H), 2.59-2.41 (m,1H), 2.40-2.00 (m, 4H), 1.91-1.51 (m, 5H), 1.42-1.32 (m, 2H), 1.15 (d, J= 6.0 Hz, 3H). LCMS (ES, m/z): 491 [M + H]⁺ 572

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.68-7.64 (m, 1H), 7.53-7.50 (m, 1H),7.43-7.40 (m, 1H), 7.08-7.05 (m, 2H), 6.39 (s, 1H), 5.01-4.95 (m, 1H),4.87-4.72 (m, 1H), 3.81 (s, 3H), 3.31-3.13 (m, 1H), 2.97-2.96 (m, 1H),2.94-2.86 (m, 1H), 2.50-2.46 (m, 1H), 2.44-2.32 (m, 1H), 2.28-2.17 (m,3H), 1.74-1.60 (m, 3H), 1.53-1.15 (m, 2H), 1.14 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 514 [M + H]⁺ 573

LCMS (ES, m/z): 511 [M + H]⁺ 574

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48 (d, J = 8.8 Hz, 1H), 7.41 (d, J =8.8 Hz, 1H), 7.27-7.14 (m, 4H), 6.92-6.90 (m, 1H), 5.15-5.04 (m, 1H),4.73-4.50 (m, 1H), 3.77 (s, 3H), 3.23-3.15 (m, 1H), 2.94-2.85 (m, 1H),2.60-2.49 (m, 1H), 2.41-2.18 (m, 5H), 1.89-1.70 (m, 2H), 1.86-1.65 (m,5H), 1.54-1.46 (m, 2H), 1.13 (d, J = 6.8 Hz, 3H) LCMS (ES, m/z): 504[M + H]⁺. 575

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.53 (d, J = 8.8 Hz, 1H), 7.39 (d, J =8.8 Hz, 1H), 4.76-4.73 (m, 2H), 3.72 (s, 3H), 3.22-3.17 (m, 1H),3.21-3.13 (m, 1H), 2.94-2.86 (m, 3H), 2.47-2.40 (m, 2H), 2.27-2.25 (m,3H), 1.94-1.89 (m, 3H), 1.76-1.62 (m, 8H), 1.48-1.29 (m, 4H), 1.17-1.02(m, 4H). LCMS (ES, m/z): 468 [M + H]⁺. 576

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.26 (d, J = 9.0 Hz, 1H), 7.15-7.10 (m,4H), 7.03-7.01 (m, 2H), 4.85-4.71 (m, 1H), 3.76-3.62 (m, 7H), 3.43 (s,2H), 3.32-3.08 (m, 4H), 2.35-1.66 (m, 8H), 1.58 (d, J = 6.6 Hz, 3H),1.45-1.30 (m, 1H), 1.12 (d, J = 6.6 Hz, 3H), 0.60-0.40 (m, 1H). LCMS(ES, m/z): 487 [M + H]+. 577

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.51-7.41 (m, 3H), 7.41-7.29 (m, 1H),7.24-7.13 (m, 1H), 7.11-6.94 (m, 1H), 6.19 (s, 1H), 4.81-4.71 (m, 2H),4.71-4.57 (m, 2H), 3.78 (s, 3H), 3.32-3.18 (m, 1H), 3.08-2.91 (m, 1H),2.82-2.67 (m, 1H), 2.39-2.18 (m, 3H), 2.16-1.98 (m, 1H), 1.82-1.68 (m,1H), 1.68-1.60 (m, 1H), 1.50-1.38 (m, 2H), 1.21-1.02 (m, 4H), 0.97-0.94(m, 1H). LCMS (ES, m/z): 501 [M + H]⁺ 578

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52-7.45 (m, 2H), 7.41-7.36 (m, 1H),7.17 (d, J = 7.2 Hz, 1H), 6.90 (t, J = 7.6 Hz, 1H), 6.28 (s, 1H),4.85-4.70 (m, 2H), 4.53-4.38 (m, 2H), 3.78 (s, 3H), 3.33-3.12 (m, 3H),2.98-2.85 (m, 2H), 2.48-2.37 (m, 1H), 2.31-2.21 (m, 2H), 2.15-1.92 (m,2H), 1.78-1.53 (m, 3H), 1.49-1.28 (m, 2H), 1.15 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 520 [M + H]⁺ 579

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.43 (s, 1H), 8.42 (s, 1H), 7.80 (d, J= 2.8 Hz, 1H), 7.52-7.46 (m, 2H), 6.72-6.10 (m, 2H), 5.62 (d, J = 9.2Hz, 1H), 4.99-4.91 (m, 1H), 4.76-4.59 (m, 1H), 3.78 (s, 3H), 3.20 (m,1H), 2.97 (m, 2H), 2.43-2.31 (m, 2H), 2.30-2.02 (m, 3H), 1.82-1.75 (m,1H), 1.72-1.60 (m, 2H), 1.21-1.02 (m, 5H). LCMS (ES, m/z): 503 [M + H]⁺580

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.32-8.23 (m, 1H), 7.93-7.85 (m, 2H),7.58 (d, J = 6.6 Hz, 1H), 7.46-7.40 (m, 4H), 7.35-7.22 (m, 1H),5.12-5.08 (m, 1H), 4.77-4.74 (m, 1H), 4.45-4.37 (m, 1H), 3.97-3.77 (m,3H), 3.78 (s, 3H), 3.52-3.48 (m, 2H), 3.20-3.18 (m, 1H), 3.04-2.88 (m,2H), 2.45-2.25 (m, 2H), 2.12-1.98 (m, 1H), 1.79 (m, 3H), 1.14 (d, J =6.6 Hz, 3H). LCMS (ES, m/z): 528 [M + H]⁺ 581

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.89-7.86 (m, 2H), 7.85-7.07 (m, 3H),4.75-4.50 (m, 4H), 3.80 (s, 3H), 3.25-3.30 (m, 2H), 2.85 (s, 6H),2.60-2.10 (m, 6H), 2.00-1.45 (m, 5H), 1.19 (d, J = 6.6 Hz, 3H). LCMS(ES, m/z): 523 [M + H]⁺ 582

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.43-7.41 (m, 1H), 7.36-7.33 (m, 3H),7.31-7.24 (m, 3H), 4.87-4.73 (m, 1H), 4.58-4.53 (m, 1H), 4.45-4.40 (m,1H), 4.22-4.14 (m, 2H), 3.76 (s, 3H), 3.30-3.26 (m, 1H), 2.99-2.95 (m,1H), 2.39-2.29 (m, 3H), 2.28-2.13 (m, 1H), 2.12-1.85 (m, 3H), 1.78-1.68(m, 1H), 1.67-1.55 (m, 1H), 1.16-1.13 (m, 4H), 1.00-0.91 (m, 1H). LCMS(ES, m/z): 492 [M + H]⁺. 583

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.84-7.80 (m, 2H), 7.66 (d, J = 2.0 Hz,1H), 7.41 (d, J = 1.6 Hz, 1H), 6.25 (m, 1H), 4.86-4.67 (m, 3H), 4.26 (m,1H), 3.80 (s, 3H), 3.17-2.99 (m, 3H), 2.31-2.22 (m, 5H), 1.89-1.85 (m,3H), 1.68-1.54 (m, 4H), 1.48 (m, 1H), 1.36-1.25 (m, 1H), 1.15 (d, J =6.8 Hz, 3H). LCMS (ES, m/z): 480 [M + H]⁺. 584

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52-7.48 (m, 5H), 7.39 (d, J = 8.8 Hz,1H), 6.93-6.60 (m, 1H), 4.82-4.66 (m, 1H), 4.58-4.56 (m, 1H), 4.38-4.35(m, 1H), 4.06-3.92 (m, 2H), 3.78-3.74 (m, 4H), 3.63-3.49 (m, 1H),3.43-3.34 (m, 2H), 3.16-3.08 (m, 1H), 2.92-2.88 (m, 1H), 2.49-2.42 (m,1H), 2.28-2.05 (m, 2H), 2.03-1.81 (m, 2H), 1.81-1.65 (m, 1H), 1.13 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 528 [M + H]⁺. 585

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.51-8.35 (m, 3H), 7.45 (d, J = 8.8 Hz,1H), 7.34 (d, J = 8.8 Hz, 1H), 4.77-4.72 (m, 2H), 3.96-3.93 (m, 1H),3.77 (s, 3H), 3.60-3.54 (m, 1H), 3.33-3.20 (m, 2H), 2.99-2.88 (m, 2H),2.45-2.22 (m, 5H), 1.84-1.54 (m, 8H), 1.14 (d, J = 6.4 Hz, 3H). LCMS(ES, m/z): 492 [M + H]⁺. 586

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.32 (s, 1H), 8.02 (s, 1H), 7.88 (s,2H), 4.98-4.89 (m, 2H), 4.78-4.71 (m, 2H), 3.84 (s, 3H), 3.05-2.95 (m,3H), 2.50-2.12 (m, 5H), 2.09-1.71 (m, 4H), 1.51-1.40 (m, 1H), 1.27 (s,9H), 1.17 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 536 [M + H]⁺ 587

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 9.16 (s, 1H), 8.08-8.97 (m, 3H),7.79-7.40 (m, 4H), 6.47 (s, 1H), 5.12 (s, 1H), 4.77-4.73 (m, 1H), 3.78(s, 3H), 3.34-3.20 (m, 1H), 2.93-2.82 (m, 2H), 2.38-2.15 (m, 5H),1.76-1.54 (m, 5H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 529 [M +H]⁺. 588

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.54-7.51 (m, 1H), 7.32-7.29 (m, 1H),5.66-5.61 (m, 1H), 4.66-4.62 (m, 1H), 3.66 (s, 3H), 3.56-3.52 (m, 1H),3.45-3.41 (m, 1H), 3.07-3.00 (m, 1H), 2.99-2.77 (m, 2H), 2.39-2.34 (m,1H), 2.24-2.20 (m, 1H), 2.20-2.11 (m, 5H), 1.68-1.51 (m, 11H), 1.35-1.15(m, 2H), 1.09 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 509 [M + H]⁺ 589

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.73 (s, 1H), 8.11 (s, 1H), 8.07-8.02(m, 1H), 7.51-7.45-7.38 (m, 2H), 7.03 (s, 1H), 6.36 (s, 1H), 4.80-4.72(m, 2H), 3.78 (s, 3H), 3.27-3.14 (m, 1H), 3.01-2.89 (m, 2H), 2.45-2.38(m, 2H), 2.28-2.20 (m, 1H), 2.12-1.98 (m, 2H), 1.76-1.73 (m, 1H),1.63-1.47 (m, 2H), 1.25-1.09 (m, 4H), 1.08-1.01 (m, 1H). LCMS (ES, m/z):519 [M + H]⁺. 590

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.45-7.35 (m, 2H), 7.34-7.19 (m, 5H),4.82-4.71 (m, 1H), 4.39 (s, 2H), 4.28-4.14 (m, 1H), 3.76 (s, 3H),3.28-3.15 (m, 1H), 3.02-2.89 (m, 1H), 2.41-2.10 (m, 4H), 2.06-1.92 (m,2H), 1.79-1.69 (m, 1H), 1.45-1.36 (m, 4H), 1.14 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 462 [M + H]⁺ 591

LCMS (ES, m/z): 491 [M + H]⁺ 592

LCMS (ES, m/z): 511 [M + H]⁺ 593

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.98-7.94 (m, 1H), 7.88-7.86 (s, 2H),7.43-7.41 (m, 1H), 7.40-7.15 (m, 1H), 6.98-6.97 (m, 1H), 5.05-5.01 (m,1H), 4.84-4.72 (m, 3H), 3.83 (s, 3H), 3.19-2.98 (m, 3H), 2.50-2.30 (m,2H), 2.30-2.10 (m, 3H), 2.00-1.70 (m, 4H), 1.42-1.30 (m, 1H), 1.18 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 529 [M + H]⁺ 594

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58-7.41 (m, 2H), 7.37-7.31 (m, 5H),4.81-4.66 (m, 2H), 4.41-4.27 (m, 1H), 4.22-4.11 (m, 1H), 4.10-4.02 (m,1H), 4.01-3.93 (m, 1H), 3.91-3.76 (m, 4H), 3.71-3.59 (m, 1H), 3.42-3.34(m, 1H), 3.23-3.14 (m, 1H), 3.04-2.89 (m, 1H), 2.87-2.63 (m, 1H),2.34-2.17 (m, 1H), 1.86-1.66 (m, 2H), 1.14 (d, J = 6.0 Hz, 3H). LCMS(ES, m/z): 514 [M + H]⁺. 595

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.86 (s, 2H), 6.84-6.68 (m, 3H),4.89-4.82 (m, 1H), 4.67 (s, 2H), 4.63-4.49 (m, 1H), 3.83 (s, 6H),3.21-2.98 (m, 2H), 2.65-2.50 (m, 1H), 2.40-2.12 (m, 5H), 2.00-1.88 (m,1H), 1.84-1.68 (m, 2H), 1.62-1.47 (m, 2H), 1.19 (d, J = 6.9 Hz, 3H).LCMS (ES, m/z): 510 [M + H]⁺. 596

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.71-7.51 (m, 1H), 7.50-7.27 (m, 1H),5.37-5.12 (m, 2H), 4.82-4.71 (m, 1H), 3.78 (s, 3H), 3.24-3.09 (m, 1H),3.03-2.88 (m, 2H), 2.59-2.41 (m, 1H), 2.41-2.13 (m, 5H), 2.11-1.91 (m,5H), 1.91-1.61 (m, 8H), 1.42-1.32 (m, 2H), 1.15 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 534 [M + H]⁺. 597

LCMS (ES, m/z): 508 [M + H]⁺ 598

LCMS (ES, m/z): 491 [M + H]⁺ 599

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.35 (s, 1H), 8.16 (d, J = 4.4 Hz, 1H),7.54-7.52 (m, 2H), 7.46-7.43 (m, 1H), 7.37-7.34 (m, 1H), 6.02-5.96 (m,1H), 4.84-4.64 (m, 2H), 3.79 (s, 3H), 3.25-3.11 (m, 1H), 3.08-2.86 (m,1H), 2.60-2.10 (m, 6H), 2.09-2.01 (m, 1H), 1.87 (d, J = 6.4 Hz, 3H),1.79-1.53 (m, 4H), 1.13 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 493 [M +H]⁺. 600

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.44-7.26 (m, 4H), 7.06-6.93 (m, 2H),6.22 (s, 1H), 4.86-4.74 (m, 1H), 4.53 (s, 2H), 4.52-4.39 (m, 1H), 3.75(s, 3H), 3.30-2.90 (m, 2H), 2.55-1.95 (m, 6H), 1.75-1.45 (m, 5H), 1.14(d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 501 [M + H]⁺. 601

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.55-7.26 (m, 3H), 7.09-6.96 (m, 3H),4.81-4.65 (m, 2H), 4.49-4.32 (m, 2H), 3.79 (s, 3H), 3.28-3.17 (m, 1H),3.03-2.96 (m, 2H), 2.45-2.10 (m, 5H), 1.81-1.68 (m, 3H), 1.33-1.20 (m,2H), 1.16 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 480 [M + H]⁺. 602

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58-7.53 (m, 1H), 7.52-7.41 (m, 1H),7.38-7.23 (m, 5H), 4.83-4.69 (m, 2H), 4.41-4.30 (m, 1H), 4.13-3.92 (m,2H), 3.91-3.76 (m, 4H), 3.75-3.62 (m, 1H), 3.25-3.10 (m, 3H), 3.02-2.76(m, 2H), 2.74-2.57 (m, 1H), 2.31-2.16 (m, 1H), 1.78-1.68 (m, 1H), 1.14(d, J = 5.6 Hz, 3H). LCMS (ES, m/z): 514 [M + H]⁺. 603

¹H NMR (400 MHz, CD₃OD) δ (ppm): 7.57 (d, J = 8.8 Hz, 1H), 7.45 (d, J =8.8 Hz, 1H), 5.17-5.08 (m, 2H), 4.77-4.74 (m, 1H), 3.95-3.89 (m, 2H),3.79 (s, 3H), 3.71-3.68 (m, 1H), 3.48-3.39 (m, 2H), 3.20-3.18 (m, 1H),3.02-3.00 (m, 1H), 2.94-2.90 (m, 1H), 2.57-2.55 (m, 1H), 2.40-2.24 (m,4H), 1.97-1.90 (m, 4H), 1.76-1.62 (m, 8H), 1.15 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 500 [M + H]⁺ 604

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.53-8.46 (m, 1H), 8.18-8.09 (m, 2H),7.50 (d, J = 9.2 Hz, 1H), 7.40 (d, J = 9.2 Hz, 1H), 5.46-5.36 (m, 1H),4.79-4.70 (m, 1H), 3.77 (s, 3H), 3.28-3.18 (m, 1H), 3.00 (s, 1H),2.96-2.87 (m, 1H), 2.53-2.41 (m, 1H), 2.32-2.19 (m, 4H), 1.87 (s, 1H),1.80-1.60 (m, 7H), 1.58-1.47 (m, 1H), 1.13 (d, J = 6.4 Hz, 3H). LCMS(ES, m/z): 506 [M + H]⁺. 605

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.51-7.38 (m, 2H), 7.30-7.21 (m, 2H),7.02 (d, J = 7.5 Hz, 2H), 6.95-6.80 (m, 1H), 5.88-5.70 (m, 1H),4.85-4.70 (m, 2H), 3.78 (s, 3H), 3.23-3.10 (m, 1H), 3.00-2.85 (m, 1H),2.55-2.30 (m, 2H), 2.30-2.15 (m, 3H), 2.19-2.03 (m, 1H), 2.03-1.97 (d, J= 12.9 Hz, 1H), 1.84 (d, J = 6.9 Hz, 3H), 1.80-1.76 (m, 1H), 1.70-1.50(m, 3H), 1.13 (d, J = 6.3 Hz, 3H). LCMS (ES, m/z): 492 [M + H]⁺. 606

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.74 (s, 1H), 7.66-7.53 (m, 2H), 7.42(d, J = 8.4 Hz, 1H), 7.29 (d, J = 3.2 Hz, 1H), 7.13 (d, J = 8.8 Hz, 1H),6.51-6.45 (m, 2H), 4.83-4.67 (m, 2H), 3.80 (s, 3H), 3.31-3.22 (m, 1H),3.11-3.00 (m, 1H), 2.36-1.78 (m, 7H), 1.62-1.54 (m, 1H), 1.39-1.25 (m,3H), 1.19 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 517 [M + H]⁺. 607

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49-7.20 (m, 7H), 4.85-4.71 (m, 2H),3.78 (s, 3H), 3.43-3.33 (m, 1H), 3.04-2.92 (m, 1H), 2.91-2.80 (m, 1H),2.41-2.25 (m, 3H), 2.10-1.99 (m, 4H), 1.97-1.82 (m, 1H), 1.75-1.62 (m,1H), 1.55-1.35 (m, 2H), 1.16 (d, J = 6.4 Hz, 3H), 1.11-0.95 (m, 1H),0.78-0.62 (m, 1H). LCMS (ES, m/z): 492 [M + H]⁺. 608

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.86-7.69 (m, 3H), 7.48 (d, J = 8.4 Hz,1H), 7.32 (d, J = 3.2 Hz, 1H), 7.17 (d, J = 7.6 Hz, 1H), 6.52-6.49 (m,2H), 4.88-4.86 (m, 1H), 4.76-4.59 (m, 1H), 3.82 (s, 3H), 3.31-3.24 (m,1H), 3.15-3.01 (m, 1H), 2.35-2.21 (m, 1H), 2.23-2.06 (m, 2H), 2.06-1.85(m, 4H), 1.73-1.69 (m, 1H), 1.48-1.40 (m, 2H), 1.27-1.22 (m, 1H), 1.21(d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 517 [M + H]⁺. 609

¹H-NMR (DMSO, 400 MHz) δ (ppm): 7.95 (s, 1H), 7.55 (s, 1H), 7.31-7.15(m, 2H), 4.62-455 (m, 1H), 4.54-4.35 (m, 2H), 4.30-4.15 (m, 1H),3.85-3.70 (m, 2H), 3.65 (s, 3H), 3.45-3.35 (m, 2H), 3.35-3.25 (m, 2H),3.12-3.01 (m, 1H), 2.85-2.75 (m, 1H), 2.20-2.01 (m, 4H), 2.00-1.91 (m,1H), 1.75-1.50 (m, 4H), 1.48-1.32 (m, 1H), 1.18 (d, J = 6.8 Hz, 3H),1.06 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 511 [M + H]⁺. 610

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.45 (s, 1H), 8.00-7.97 (m, 1H),7.89-7.87 (m, 1H), 7.82-7.45 (m, 2H), 6.46 (s, 1H), 5.11-5.05 (m, 1H),4.87-4.83 (m, 1H), 3.82 (s, 3H), 3.18-3.12 (m, 1H), 3.03-2.94 (m, 2H),2.45-2.11 (m, 5H), 1.94-1.73 (m, 4H), 1.52-1.48 (m, 1H), 1.18 (d, J =6.8 Hz, 3H). LCMS (ES, m/z): 513 [M + H]⁺. 611

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.68 (s, 1H), 8.51 (s, 1H), 7.97-7.86(m, 2H), 5.5.11-4.85 (m, 4H), 3.84 (s, 3H), 3.13-2.97 (m, 4H), 2.50-2.35(m, 2H), 2.33-2.17 (m, 3H), 1.97-1.76 (m, 4H), 1.52-1.38 (m, 1H),1.22-1.13 (m, 9H). LCMS (ES, m/z): 506 [M + H]⁺. 612

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.05 (s, 1H), 8.01 (s, 1H), 7.51-7.46(m, 2H), 7.42-7.38 (m, 2H), 6.37 (s, 1H), 5.00-4.98 (m, 1H), 4.80-4.75(m, 1H), 3.78 (s, 3H), 3.27-3.20 (m, 1H), 3.02-2.98 (m, 1H), 2.89-2.84(m, 1H), 2.38-2.36 (m, 2H), 2.31-2.25 (m, 1H), 2.11-1.97 (m, 2H),1.79-1.76 (m, 1H), 1.56-1.41 (m, 2H), 1.20-1.16 (m, 1H), 1.15 (d, J =6.8 Hz, 3H), 0.99-0.96 (m, 1H). LCMS (ES, m/z): 518 [M + H]⁺. 613

LCMS (ES, m/z): 495 [M + H]⁺ 614

¹H NMR (400 MHz, CD₃OD) δ (ppm): 7.55 (d, J = 8.8 Hz, 1H), 7.41 (d, J =8.8 Hz, 1H), 4.83-4.76 (m, 2H), 3.79 (s, 3H), 3.53-3.48 (m, 1H),3.23-3.17 (m, 1H), 3.15-3.14 (m, 1H), 2.99-2.89 (m, 1H), 2.79-2.73 (m,1H), 2.46-2.41 (m, 2H), 2.39-2.24 (m, 3H), 2.01-1.99 (m, 1H), 1.93-1.91(m, 2H), 1.77-1.59 (m, 7H), 1.34-1.30 (m, 2H), 1.21-1.14 (m, 6H). LCMS(ES, m/z): 484 [M + H]⁺ 615

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.65-7.48 (m, 1H), 7.48-7.22 (m, 1H),5.13-4.94 (m, 1H), 4.82-4.67 (m, 2H), 3.78 (s, 3H), 3.29-3.12 (m, 1H),3.08-2.82 (m, 2H), 2.61-2.19 (m, 6H), 2.19-2.01 (m, 1H), 2.01-1.82 (m,2H), 1.82-1.46 (m, 12H), 1.42-1.32 (m, 2H), 1.15 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 498 [M + H]⁺. 616

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48-7.45 (m, 1H), 7.40-7.38 (m, 1H),7.30-7.23 (m, 3H), 7.18-7.17 (m, 1H), 4.77-4.68 (m, 2H), 4.44-4.40 (m,1H), 4.33-4.29 (m, 1H), 3.76 (s, 3H), 3.19-3.15 (m, 1H), 2.98-2.94 (m,2H), 2.33-2.13 (m, 5H), 1.76-1.64 (m, 3H), 1.24-1.23 (m, 2H), 1.13 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 496 [M + H]⁺. 617

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.93 (s, 1H), 7.56-7.33 (m, 3H),5.22-5.03 (m, 1H), 4.81-4.65 (m, 1H), 3.76 (s, 3H), 3.26-3.07 (m, 1H),3.02-2.87 (m, 1H), 2.56-2.37 (m, 1H), 2.37-2.07 (m, 5H), 1.96-1.86 (m,2H), 1.78-1.52 (m, 7H), 1.11 (d, J = 6.9 Hz, 3H). LCMS (ES, m/z): 512[M + H]⁺ 618

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.60 (d, J = 8.8 Hz, 1H), 7.40 (d, J =9.2 Hz, 1H), 7.24-7.15 (m, 3H), 7.22-7.16 (m, 2H), 5.85-5.77 (m, 1H),4.78-7.65 (m, 1H), 3.79 (s, 3H), 3.45-3.33 (m, 2H), 3.22-3.01 (m, 2H),2.88-2.64 (m, 2H), 2.57-2.49 (m, 1H), 2.45-2.20 (m, 3H), 2.11-2.01 (m,1H), 1.82-1.78 (m, 3H), 1.75 (s, 3H), 1.74-1.65 (m, 1H), 1.15 (d, J =6.8 Hz, 3H). LCMS (ES, m/z): 506 [M + H]+. 619

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.18 (s, 1H), 7.79-7.65 (m, 1H),7.57-7.30 (m, 3H), 6.93 (d, J = 8.0 Hz, 1H), 4.84-4.66 (m, 2H),4.44-4.36 (m, 2H), 3.79 (s, 3H), 3.28-3.12 (m, 1H), 3.05-2.91 (m, 2H),2.43-2.10 (m, 5H), 1.84-1.65 (m, 3H), 1.56-1.30 (m, 2H), 1.15 (d, J =6.4 Hz, 1H). LCMS (ES, m/z): 529 [M + H]⁺. 620

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49 (d, J = 9.2 Hz, 1H), 7.38 (d, J =9.2 Hz, 1H), 7.17 (d, J = 8.0 Hz, 2) 7.00 (d, J = 8.0 Hz, 2H), 4.74-4.73(m, 1H), 4.42-4.35 (m, 1H), 4.42-4.23 (m, 1H), 3.94-3.87 (m, 2H), 3.76(s, 3H), 3.73-3.50 (m, 2H), 3.35-3.30 (m, 1H), 3.29-3.03 (m, 2H),2.93-2.88 (m, 1H), 2.52-2.31 (m, 1H), 2.30-2.19 (m, 1H), 2.14-2.01 (m,1H), 1.98-1.80 (m, 3H), 1.80-1.70 (m, 1H), 1.11 (d, J = 6.8 Hz, 3H),0.92-0.89 (m, 2H), 0.65-0.61 (m, 2H). LCMS (ES, m/z): 518 [M + H]⁺. 621

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.79 (d, J = 7.6 Hz, 1H), 7.64-7.43 (m,4H), 7.15-7.13 (m, 1H), 4.83-4.61 (m, 4H), 3.79 (s, 3H), 3.28-2.92 (m,3H), 2.41-2.17 (m, 5H), 1.79-1.66 (m, 4H), 1.47-1.37 (m, 1H), 1.16 (d, J= 6.0 Hz, 3H). LCMS (ES, m/z): 487 [M + H]⁺. 622

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.65-7.58 (m, 1H), 7.48-7.42 (m, 1H),4.81-4.70 (m, 1H), 3.96-3.86 (m, 2H), 3.79 (s, 3H), 3.55-3.43 (m, 1H),3.43-3.35 (m, 2H), 3.28-3.13 (m, 1H), 3.13-2.99 (m, 2H), 2.99-2.84 (m,1H), 2.56-2.38 (m, 2H), 2.33-2.16 (m, 3H), 2.02-1.86 (m, 3H), 1.86-1.53(m, 7H), 1.48 (d, J = 6.8 Hz, 3H), 1.40-1.20 (m, 2H), 1.15 (d, J = 6.4Hz, 3H). LCMS (ES, m/z): 498 [M + H]⁺. 623

¹H NMR (400 MHz, CD₃OD) δ (ppm): 7.51 (d, J = 8.8 Hz, 1H), 7.39 (d, J =9.2 Hz, 1H), 4.77-4.72 (m, 1H), 4.59-4.52 (m, 2H), 3.78 (s, 3H),3.63-3.56 (m, 4H), 3.25-3.23 (m, 1H), 3.02-2.99 (m, 1H), 2.94-2.90 (m,1H), 2.50-2.48 (m, 1H), 2.33-2.24 (m, 4H), 1.92-1.85 (m, 2H), 1.77-1.74(m, 7H), 1.72-1.55 (m, 5H), 1.14 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z):511 [M + H]⁺ 624

¹H NMR (400 MHz, CD₃OD) δ (ppm): 7.52 (d, J = 8.8 Hz, 1H), 7.39 (d, J =9.2 Hz, 1H), 4.83-4.72 (m, 2H), 4.56-4.52 (m, 1H), 3.79 (s, 3H),3.68-3.60 (m, 1H), 3.56-3.45 (m, 3H), 3.23-3.17 (m, 1H), 3.01-2.98 (m,1H), 2.95-2.89 (m, 1H), 2.50-2.48 (m, 1H), 2.36-2.24 (m, 4H), 1.89-1.86(m, 2H), 1.77-1.44 (m, 11H), 1.28-1.23 (m, 1H), 1.14 (d, J = 6.8 Hz,3H). LCMS (ES, m/z): 511 [M + H]⁺ 625

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.60-7.53 (m, 1H), 7.45-7.39 (m, 1H),5.07-4.97 (m, 1H), 4.80-4.69 (m, 2H), 3.79 (s, 3H), 3.27-3.15 (m, 1H),3.01-2.86 (m, 2H), 2.53-2.13 (m, 6H), 2.08-2.00 (m, 1H), 1.96-1.80 (m,3H), 1.80-1.73 (m, 5H), 1.35-1.22 (m, 4H), 1.21-1.12 (m, 5H). LCMS (ES,m/z): 484 [M + H]⁺. 626

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49 (d, J = 9.2 Hz, 1H), 7.35 (d, J =8.8 Hz, 1H), 7.15-7.00 (m, 2H), 6.90-6.81 (m, 1H), 4.79-4.65 (m, 1H),4.49-4.31 (m, 1H), 3.79 (s, 3H), 3.69-3.57 (m, 1H), 3.33-3.05 (m, 5H),3.00-2.88 (m, 1H), 2.88-2.75 (m, 1H), 2.76-2.65 (m, 1H), 2.48-2.23 (m,3H), 1.81-1.65 (m, 2H), 1.51 (d, J = 6.8 Hz, 3H), 1.15 (d, J = 6.4 Hz,3H), 1.10-0.96 (m, 1H). LCMS (ES, m/z): 483 [M + H]⁺. 627

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.84-7.74 (m, 2H), 7.64 (d, J = 2.0 Hz,1H), 7.41 (s, 1H), 6.28-6.26 (m, 1H), 4.78-4.63 (m, 2H), 4.61-4.41 (m,1H), 4.41-4.26 (m, 1H), 3.81 (s, 3H), 3.20-2.99 (m, 2H), 2.63-2.46 (m,1H), 2.42-2.11 (m, 5H), 2.08-1.94 (m, 1H), 1.94-1.82 (m, 1H), 1.82-1.68(m, 1H), 1.68-1.42 (m, 5H), 1.32-1.21 (m, 1H), 1.16 (d, J = 6.8 Hz, 3H).LCMS: (ES, m/z): 480 [M + H]⁺. 628

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.95-7.81 (m, 3H), 7.39 (s, 1H),4.87-4.67 (m, 3H), 3.86-3.71 (m, 5H), 3.12-2.91 (m, 3H), 2.53-2.36 (m,3H), 2.36-2.15 (m, 2H), 2.01-1.79 (m, 4H), 1.69-1.51 (m, 1H), 1.17 (d, J= 6.9 Hz, 3H). LCMS (ES, m/z): 500 [M + H]⁺. 629

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56-7.45 (m, 5H), 7.40 (d, J = 9.2 Hz,1H), 6.91-6.53 (m, 1H), 4.86-4.68 (m, 2H), 4.40-4.27 (m, 1H), 4.19-4.04(m, 2H), 4.03-3.92 (m, 1H), 3.91-3.80 (m, 1H), 3.79 (s, 3H), 3.73-3.61(m, 1H), 3.31-3.27 (m, 1H), 3.23-3.11 (m, 1H), 2.99-2.89 (m, 1H),2.87-2.71 (m, 1H), 2.32-2.18 (m, 1H), 1.90-1.78 (m, 1H), 1.77-1.66 (m,1H), 1.13 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 564 [M + H]⁺. 630

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.86-7.73 (m, 1H), 7.58-7.48 (m, 1H),7.48-7.34 (m, 1H), 7.34-7.23 (m, 1H), 6.99-6.84 (m, 1H), 6.37 (s, 1H),5.08-4.92 (m, 1H), 4.81-4.61 (m, 1H), 3.78 (s, 3H), 3.64 (s, 3H),3.27-3.04 (m, 1H), 3.01-2.93 (m, 1H), 2.93-2.82 (m, 1H), 2.59-2.39 (m,1H), 2.39-2.28 (m, 1H), 2.28-2.07 (m, 3H), 1.85-1.60 (m, 3H), 1.59-1.38(m, 2H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 542 [M + H]⁺ 631

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 9.17 (s, 1H), 8.26-8.02 (m, 3H),7.82-7.50 (m, 4H), 6.51 (s, 1H), 5.08-4.75 (m, 2H), 3.78 (s, 3H),3.33-3.15 (m, 1H), 2.99-2.77 (m, 2H), 2.45-2.02 (m, 5H), 1.75-1.48 (m,3H), 1.15 (d, J = 6.4 Hz, 3H), 1.12-1.07 (m, 2H). LCMS (ES, m/z): 529[M + H]⁺. 632

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51-7.47 (m, 1H), 7.42-7.38 (m, 3H),7.34-7.25 (m, 3H), 4.79-4.71 (m, 2H), 4.32-4.30 (m, 1H), 3.76 (s, 3H),3.75-3.67 (m, 2H), 3.40 (s, 3H), 3.27-3.22 (m, 1H), 3.14-3.12 (m, 1H),2.90-2.86 (m, 1H), 2.37-2.21 (m, 3H), 2.09-2.05 (m, 1H), 1.96-1.86 (m,3H), 1.75-1.69 (m, 2H), 1.54-1.50 (m, 1H), 1.12 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 506 [M + H]+. 633

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.59-7.45 (m, 2H), 7.39-7.29 (m, 2H),7.10 (m, 2H), 7.02 (m, 1H), 5.42 (s, 2H), 4.78 (m, 1H), 4.51 (m, 1H),3.79 (s, 3H), 3.19 (m, 1H), 2.97 (m, 1H), 2.55-2.44 (m, 1H), 2.43-2.20(m, 5H), 2.03 (m, 2H), 1.77 (m, 1H), 1.62 (m, 2H), 1.15 (d, J = 6.4 Hz,3H). LCMS (ES, m/z): 478 [M + H]⁺. 634

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55 (d, J = 9.2 Hz, 1H), 7.44 (d, J =8.8 Hz, 1H), 5.22-5.03 (m, 1H), 4.82-4.64 (m, 3H), 3.79 (s, 3H),3.31-3.26 (m, 2H), 3.25-3.11 (m, 1H), 3.01-2.87 (m, 2H), 2.73-2.59 (m,1H), 2.55-2.40 (m, 2H), 2.32-2.19 (m, 4H), 2.02-1.89 (m, 6H), 1.88-1.78(m, 4H), 1.77-1.56 (m, 3H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):523 [M + H]⁺. 635

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.92-7.81 (m, 2H), 5.13-5.02 (m, 1H),4.89-4.81 (m, 1H), 3.96-3.88 (m, 2H), 3.83 (s, 3H), 3.52-3.35 (m, 2H),3.32-3.25 (m, 1H), 3.15-2.90 (m, 3H), 2.52-2.45 (m, 2H), 2.38-2.26 (m,3H), 2.24-2.06 (m, 1H), 2.00-1.80 (m, 5H), 1.72-1.45 (m, 5H), 1.18 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 470 [M + H]⁺. 636

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.89 (s, 1H), 7.62-7.62 (m, 1H),7.62-7.52 (m, 1H), 7.47-7.45 (m, 1H), 6.22 (s, 1H), 4.92-4.90 (m, 1H),4.82-4.72 (m, 1H), 4.70-4.45 (m, 2H), 3.79 (s, 3H), 3.43-3.34 (m, 1H),3.34-3.17 (m, 2H), 3.02-2.92 (m, 2H), 2.51-2.32 (m, 1H), 2.30-2.09 (m,3H), 2.01-1.97 (m, 1H), 1.82-1.78 (m, 3H), 1.72-1.40 (m, 2H), 1.16 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 521 [M + H]⁺. 637

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58-7.51 (m, 1H), 7.44-7.37 (m, 1H),5.23-5.16 (m, 1H), 4.80-4.72 (m, 1H), 4.72-4.65 (m, 1H), 3.79 (s, 3H),3.24-3.12 (m, 1H), 3.00-2.85 (m, 2H), 2.53 (td, J = 13.2, 5.5 Hz, 1H),2.37-2.20 (m, 6H), 2.01-1.93 (m, 1H), 1.90-1.63 (m, 7H), 1.52-1.41 (m,1H), 1.36-1.18 (m, 2H), 1.17-0.97 (m, 6H). LCMS (ES, m/z): 484 [M + H]⁺.638

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.62-7.51 (m, 1H), 7.49-7.34 (m, 1H),7.31-7.11 (m, 1H), 6.91-6.78 (m, 1H), 6.58 (s, 1H), 4.89-4.81 (m, 1H),4.78-4.66 (m, 1H), 3.83 (s, 3H), 3.78 (s, 3H), 3.27-3.12 (m, 1H),3.01-2.89 (m, 1H), 2.89-2.76 (m, 1H), 2.54-2.41 (m, 1H), 2.41-2.27 (m,1H), 2.27-2.12 (m, 3H), 2.12-2.02 (m, 1H), 1.95-1.83 (m, 1H), 1.78-1.61(m, 3H), 1.14 (d, J = 6.4 Hz, 3H), LCMS (ES, m/z): 544 [M + H]⁺. 639

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.88-7.84 (m, 1H), 7.47-7.38 (m, 2H),7.08-7.04 (m, 2H), 4.80-4.50 (m, 2H), 4.40 (s, 2H), 4.35-4.15 (m, 1H),3.75 (s, 3H), 3.25-3.10 (m, 1H), 3.00-2.90 (m, 1H), 2.50-2.00 (m, 7H),1.75-1.40 (m, 6H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 537 [M +H]⁺. 640

¹H NMR (CD₃OD, 300 MHz) δ (ppm): 7.40-7.19 (m, 7H), 4.84-4.68 (m, 1H),4.50-4.42 (m, 1H), 3.97 (d, J = 10.4 Hz, 1H), 3.74 (s, 3H), 3.31-3.25(m, 1H), 3.05-2.88 (m, 2H), 2.41-2.25 (m, 3H), 2.25-1.91 (m, 6H),1.72-1.64 (m, 1H), 1.14 (t, J = 6.3 Hz, 6H), 0.92-0.88 (m, 4H). LCMS(ES, m/z): 504 [M + H]⁺. 641

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.43 (d, J = 9.2 Hz, 1H), 7.33 (d, J =8.8 Hz, 1H), 6.96 (s, 1H), 6.94-6.76 (m, 2H), 4.97-4.88 (m, 1H),4.80-4.68 (m, 1H), 4.37-4.25 (m, 2H), 3.83-3.71 (m, 9H), 3.26-3.14 (m,1H), 3.00-2.88 (m, 1H), 2.76-2.74 (m, 1H), 2.34-2.13 (m, 4H), 2.10-1.93(m, 1H), 1.78-1.67 (m, 1H), 1.61-1.45 (m, 2H), 1.42-1.25 (m, 1H),1.18-1.03 (m, 4H). LCMS (ES, m/z): 522 [M + H]⁺. 642

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58-7.39 (m, 3H), 6.82 (d, J = 7.2 Hz,1H), 6.54 (d, J = 8.4 Hz, 1H), 5.20-5.17 (m, 1H), 4.81-4.77 (m, 2H),4.45-4.42 (m, 2H), 3.79 (s, 3H), 3.24-3.16 (m, 1H), 2.97-2.92 (m, 2H),2.36-2.19 (m, 5H), 1.78-1.71 (m, 3H), 1.42 (m, 2H), 1.22 (d, J = 6.0 Hz,3H), 1.16 (t, J = 6.4 Hz, 6H). LCMS (ES, m/z): 521 [M + H]⁺ 643

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.88 (s, 1H), 7.58-7.40 (m, 3H),5.90-5.75 (m, 1H), 5.60-5.48 (m, 1H), 4.80-4.65 (m, 2H), 3.80 (s, 3H),3.25-2.75 (m, 3H), 2.40-2.10 (m, 5H), 1.75-1.45 (m, 5H), 1.12 (d, J =6.6 Hz, 3H) LCMS (ES, m/z): 486 [M + H]⁺. 644

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48 (d, J = 9.2 Hz, 1H), 7.36 (d, J =8.8 Hz, 1H), 7.23-7.11 (m, 2H), 7.12-7.03 (m, 2H), 4.80-4.67 (m, 1H),4.52-4.38 (m, 1H), 4.26-4.15 (m, 1H), 3.98-3.87 (m, 2H), 3.76 (s, 3H),3.71-3.59 (m, 1H), 3.59-3.44 (m, 1H), 3.35-3.33 (m, 1H), 3.21-3.05 (m,2H), 2.98-2.85 (m, 1H), 2.52-2.34 (m, 1H), 2.30 (s, 3H), 2.28-2.16 (m,1H), 2.07-2.01 (m, 1H), 1.97-1.79 (m, 2H), 1.78-1.66 (m, 1H), 1.11 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 492 [M + H]⁺. 645

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.62 (s, 1H), 8.53 (s, 1H), 7.53 (d, J= 9.3 Hz, 1H), 7.40 (d, J = 9.0 Hz, 1H), 4.87 (s, 1H), 4.75-4.73 (m,1H), 3.76 (s, 3H), 3.31-3.29 (m, 1H), 2.92-2.86 (m, 2H), 2.33-2.20 (m,6H), 1.75-1.69 (m, 6H), 1.13 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 498[M + H]⁺. 646

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.50-7.20 (m, 7H), 4.80-4.60 (m, 1H),4.02-3.80 (m, 1H), 3.79 (s, 3H), 3.40-3.30 (m, 1H), 3.01-2.80 (m, 1H),2.40-2.25 (m, 2H), 2.22-2.12 (m, 2H), 2.00-1.90 (m, 2H), 1.85 (s, 6H),1.78-1.60 (m, 1H), 1.45-1.35 (m, 2H), 1.15 (d, J = 6.8 Hz, 3H),1.12-0.97 (m, 2H). LCMS (ES, m/z): 490 [M + H]⁺. 647

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.58-7.50 (m, 3H), 7.43-7.32 (m, 3H),7.32-7.24 (m, 1H), 5.25-5.18 (m, 1H), 5.05-4.94 (m, 1H), 4.82-4.71 (m,1H), 3.79 (s, 3H), 3.50-3.40 (m, 1H), 3.30-3.23 (m, 1H), 3.23-3.14 (m,1H), 2.99-2.88 (m, 2H), 2.41-2.32 (m, 2H), 2.31-2.18 (m, 3H), 1.97-1.84(m, 2H), 1.81-1.70 (m, 2H), 1.69-1.56 (m, 1H), 1.15 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 492 [M + H]⁺. 648

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.52 (d, J = 9.0 Hz, 1H), 7.38 (d, J =9.0 Hz, 1H), 4.86-4.73 (m, 2H), 3.98-3.95 (m, 2H), 3.78 (m, 3H),3.49-3.40 (m, 2H), 3.34-3.11 (m, 1H), 3.07-2.87 (m, 4H), 2.45-2.24 (m,5H), 1.94-1.63 (m, 10H), 1.43-1.38 (m, 2H), 1.14 (d, J = 6.6 Hz, 3H).LCMS (ES, m/z): 484 [M + H]⁺. 649

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.90 (s, 2H), 7.42-7.38 (m, 1H),7.15-7.10 (m, 1H), 6.51 (s, 1H), 5.09-5.02 (m, 1H), 4.88-4.86 (m, 1H),3.83 (s, 3H), 3.72 (s, 3H), 3.24-2.94 (m, 3H), 2.53-2.49 (m, 1H),2.31-2.12 (m, 4H), 1.92-1.89 (m, 1H), 1.81-1.71 (m, 2H), 1.56-1.37 (m,2H), 1.19 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 544 [M + H]⁺. 650

¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.83-7.80 (m, 1H), 7.40-7.38 (m, 1H),7.26-7.17 (m, 3H), 4.83-4.15 (m, 4H), 3.83 (s, 4H), 3.58-3.50 (m, 1H),3.16 (s, 4H), 2.96 (s, 1H), 2.33-1.91 (m, 7H), 1.36-1.26 (m, 2H), 1.14(d, J = 6.3 Hz, 3H). LCMS (ES, m/z): 510 [M + H]⁺. 651

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.58-7.42 (m, 4H), 5.60-5.40 (m, 1H),4.90-4.44 (m, 3H), 4.02-3.91 (m, 1H), 3.77 (s, 3H), 3.65-3.15 (m, 5H),2.98-2.80 (m, 2H), 2.62-2.52 (m, 1H), 2.32-2.18 (m, 1H), 1.75-1.68 (m,1H), 1.43 (d, J = 6.9 Hz, 3H), 1.13 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z):506 [M + H]⁺. 652

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.32-8.30 (m, 1H), 8.20-8.09 (m, 2H),7.57 (d, J = 9.2 Hz, 1H), 7.46 (d, J = 9.2 Hz, 1H), 7.09 (t, J = 7.2 Hz,1H), 5.46-5.30 (m, 1H), 4.81-4.70 (m, 1H), 3.95 (s, 3H), 3.78 (s, 3H),3.27-3.09 (m, 2H), 3.02-2.89 (m, 1H), 2.56-2.19 (m, 4H), 2.13-1.42 (m,10H), 1.10 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 518 [M + H]⁺. 653

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48-7.26 (m, 2H), 7.12-6.89 (m, 3H),4.80-4.70 (m, 1H), 4.65-4.52 (d, J = 7.6 Hz, 1H), 4.32-4.21 (m, 1H),3.85 (s, 3H), 3.79 (s, 3H), 3.12-2.91 (m, 1H), 2.49-2.19 (m, 3H),2.20-2.00 (m, 2H), 2.00-1.89 (m, 1H), 1.88-1.62 (m, 5H), 1.61-1.47 (m,1H), 1.45-1.27 (m, 2H), 1.17 (d, J = 6.4 Hz, 3H), 1.11-0.96 (m, 1H).LCMS (ES, m/z): 524 [M + H]⁺. 654

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.05-7.93 (s, 1H), 7.64 (d, J = 4.0 Hz,1H), 7.52-7.49 (m, 1H), 7.42-7.31 (m, 1H), 6.17 (s, 1H), 4.82-4.71 (m,2H), 4.70-4.45 (m, 2H), 3.78 (s, 3H), 3.21 (m, 1H), 3.29-3.27 (m, 1H),3.20-3.15 (m, 1H), 3.05-2.94 (m, 2H), 2.50-2.31 (m, 2H), 2.26-2.20 (m,1H), 2.16-2.03 (m, 2H), 1.74-1.70 (m, 1H), 1.70-1.61 (m, 2H), 1.33 (m,1H), 1.21-1.11 (m, 4H). LCMS (ES, m/z): 521 [M + H]⁺. 655

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.51-7.39 (m, 1H), 7.39-7.24 (m, 2H),7.19-7.01 (m, 1H), 4.81-4.63 (m, 1H), 4.63-4.48 (m, 1H), 4.43-4.38 (m,1H), 4.24-4.18 (m, 1H), 4.01-3.81 (m, 1H), 3.76 (s, 3H), 3.29-3.11 (m,1H), 3.02-2.82 (m, 1H), 2.62-2.39 (m, 1H), 2.39-2.01 (m, 5H), 2.00-1.80(m, 4H), 1.80-1.51 (m, 3H), 1.43 (d, J = 6.9 Hz, 3H), 1.15 (d, J = 6.9Hz, 3H). LCMS: (ES, m/z): 494 [M + H]⁺. 656

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.87 (d, J = 9.3 Hz, 1H), 7.62 (d, J =9.3 Hz, 1H), 7.11 (s, 1H), 7.05-6.97 (m, 2H), 4.78-4.51 (m, 4H), 3.77(s, 3H), 3.71 (s, 3H), 3.14-2.87 (m, 2H), 2.61-2.53 (m, 1H), 2.29-2.07(m, 3H), 2.04-1.95 (m, 2H), 1.86-1.74 (m, 1H), 1.65-1.41 (m, 4H), 1.09(d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 526 [M + H]⁺. 657

¹H NMR (400 MHz, CD₃OD) δ (ppm): 7.55 (d, J = 8.8 Hz, 1H), 7.42 (d, J =8.8 Hz, 1H), 4.81-4.76 (m, 2H), 3.79 (s, 3H), 3.58-3.53 (m, 1H),3.33-3.23 (m, 2H), 3.17-3.14 (m, 1H), 2.94-2.89 (m, 1H), 2.74-2.68 (m,1H), 2.49-2.30 (m, 2H), 2.28-2.24 (m, 3H), 2.02-1.92 (m, 1H), 1.79-1.76(m, 3H), 1.75-1.73 (m, 3H), 1.64-1.62 (m, 3H), 1.41-1.21 (m, 3H),1.16-1.12 (m, 4H). LCMS (ES, m/z): 484 [M + H]⁺ 658

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53-7.45 (m, 1H), 7.45-7.31 (m, 5H),7.31-7.23 (m, 1H), 5.20-5.09 (m, 1H), 4.81-4.72 (m, 1H), 4.36-4.22 (m,1H), 3.79 (s, 3H), 3.51-3.39 (m, 1H), 3.38-3.36 (m, 1H), 3.24-3.13 (m,1H), 2.99-2.90 (m, 1H), 2.51-2.47 (m, 1H), 2.38-2.11 (m, 4H), 2.11-2.02(m, 1H), 2.02-1.90 (m, 1H), 1.83-1.70 (m, 1H), 1.70-1.61 (m, 1H),1.61-1.45 (m, 1H), 1.29-1.22 (m, 1H), 1.14 (d, J = 6.8 Hz, 3H). LCMS(ES, m/z): 492 [M + H]⁺. 659

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.48-7.39 (m, 2H), 7.36-7.30 (m, 2H),6.95-7.02 (m, 1H), 6.87 (d, J = 7.8 Hz, 2H), 4.78-4.73 (m, 1H),4.17-4.07 (m, 1H), 3.80 (s, 3H), 3.47 (s, 3H), 3.20-3.12 (m, 1H),2.94-2.87 (m, 1H), 2.42-2.26 (m, 4H), 2.23-2.06 (m, 2H), 1.81-1.70 (m,3H), 1.38-1.31 (m, 2H), 1.17 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 477[M + H]⁺. 660

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.69-7.44 (m, 2H), 7.44-7.29 (m, 1H),7.12-6.99 (m, 1H), 6.98-6.82 (m, 1H), 6.37 (s, 1H), 5.03-4.91 (m, 1H),4.81-4.69 (m, 1H), 3.78 (s, 3H), 3.61 (s, 3H), 3.22-3.04 (m, 1H),3.02-2.87 (m, 2H), 2.54-2.41 (m, 1H), 2.41-2.27 (m, 1H), 2.27-2.08 (m,3H), 1.82-1.58 (m, 3H), 1.58-1.41 (m, 2H), 1.14 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 526 [M + H]⁺ 661

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.85 (s, 2H), 7.28-7.16 (m, 3H),4.90-4.89 (m, 1H), 4.68 (s, 2H), 4.56-4.54 (m, 1H), 3.87 (d, J = 2.7 Hz,3H), 3.83 (s, 3H), 3.12-3.04 (m, 2H), 2.56-2.51 (m, 1H), 2.39-2.29 (m,3H), 2.26-2.15 (m, 2H), 1.96-1.91 (m, 1H), 1.90-1.73 (m, 2H), 1.69-1.50(m, 2H), 1.18 (d, J = 6.9 Hz, 3H). LCMS (ES, m/z): 510 [M + H]⁺. 662

¹H NMR (CD₃OD, 400 MHz) δ (ppm): δ 7.61 (m, 1H), 7.52-7.42 (m, 2H),7.05-6.98 (m, 1H), 6.90-6.85 (m, 1H), 6.32 (s, 1H), 4.96-4.85 (m, 1H),4.81-4.76 (m, 1H), 4.49-4.43 (m, 1H), 3.79 (s, 3H), 3.20-3.16 (m, 1H),2.98-2.85 (m, 2H), 2.51-2.35 (m, 2H), 2.29-2.07 (m, 3H), 1.78-1.60 (m,3H), 1.50-1.39 (m, 2H), 1.18 (d, J = 6.8 Hz, 3H), 1.12 (d, J = 6.0 Hz,3H), 0.65 (d, J = 6.0 Hz, 3H). LCMS (ES, m/z): 554 [M + H]⁺. 663

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.44 (s, 1H), 7.79 (d, J = 2.4 Hz, 1H),7.54 (d, J = 2.4 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 7.35 (d, J = 8.8 Hz,1H), 4.90-4.85 (m, 1H), 4.80-4.75 (m, 2H), 4.57-4.54 (m, 1H), 3.79 (s,3H), 3.23-3.15 (m, 1H), 2.98-2.92 (m, 2H), 2.41-2.28 (m, 5H), 1.65-1.80(m, 4H), 1.46-1.43 (m, 1H), 1.16 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):497 [M + H]⁺. 664

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.93-7.85 (m, 1H), 7.74-7.60 (m, 3H),7.46-7.36 (m, 2H), 4.80-4.50 (m, 4H), 3.85-3.69 (m, 6H), 3.15-2.89 (m,4H), 2.18-1.94 (m, 7H), 1.82 (s, 1H), 1.56-1.42 (m, 4H), 1.16-1.06 (m,3H). LCMS (ES, m/z): 545 [M + H]⁺. 665

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.56 (s, 1H), 8.50 (s, 1H), 7.94-7.83(m, 2H), 4.99 (s, 2H), 4.87-4.76 (m, 2H), 3.84 (s, 3H), 3.14-2.99 (m,3H), 2.48-2.34 (m, 2H), 2.31-2.18 (m, 3H), 2.17-2.08 (m, 1H), 1.95-1.75(m, 4H), 1.52-1.40 (m, 1H), 1.7 (d, J = 6.8 Hz, 3H), 1.03-0.95 (m, 2H),0.78-1.72 (m, 2H). LCMS (ES, m/z): 504 [M + H]⁺. 666

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.52-7.31 (m, 2H), 7.28-6.01 (m, 4H),4.83-4.69 (m, 1H), 4.67-3.90 (m, 1H), 3.85-3.61 (m, 4H), 3.33-3.20 (m,1H), 3.10-2.81 (m, 2H), 2.55-2.10 (m, 5H), 1.98-1.55 (m, 6H), 1.41-1.25(m, 4H), 1.14 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 531 [M + H]⁺. 667

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51 (d, J = 9.2 Hz, 1H), 7.38 (d, J =8.8 Hz, 1H), 4.81-4.68 (m, 2H), 4.02-3.91 (m, 1H), 3.78 (s, 3H),3.55-3.38 (m, 2H), 3.26-3.10 (m, 2H), 3.07-2.93 (m, 2H), 2.52-2.34 (m,2H), 2.33-2.15 (m, 3H), 2.12-1.89 (m, 3H), 1.88-1.79 (m, 2H), 1.78-1.63(m, 4H), 1.62-1.45 (m, 3H), 1.42-1.25 (m, 2H), 1.14 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 484 [M + H]⁺. 668

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.88-7.80 (m, 2H), 7.48-7.34 (m, 5H),5.16-5.00 (m, 2H), 4.87-4.82 (m, 1H), 4.80-4.70 (m, 1H), 4.55-4.47 (m,1H), 3.83 (s, 3H), 3.22-2.97 (m, 3H), 2.54-2.42 (m, 1H), 2.32-2.13 (m,4H), 1.99-1.87 (m, 1H), 1.82-1.68 (m, 2H), 1.49-1.39 (m, 1H), 1.34-1.23(m, 1H), 1.18 (d, J = 6.8H, 3H). LCMS (ES, m/z): 492 [M + H]⁺. 669

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.56 (S, 1H), 8.50 (S, 1H), 7.55 (d, J= 9.0 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 4.89-4.68 (m, 4H), 3.78 (s,3H), 3.24-3.09 (m, 1H), 2.97-2.80 (m, 2H), 2.45-2.13 (m, 5H), 1.86-1.60(m, 4H), 1.60-1.41 (m, 1H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):498 [M + H]⁺. 670

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.95-7.75 (m, 2H), 7.75-7.71 (m, 1H),7.78-7.72 (m, 2H), 7.65-7.61 (m, 1H), 7.55-7.51 (m, 1H), 4.98-4.86 (m,1H), 4.81-4.75 (m, 1H), 3.79 (s, 3H), 3.32 (s, 3H), 3.13-2.96 (m, 2H),2.89-2.79 (m, 1H), 2.51-2.48 (m, 1H), 2.45-2.20 (m, 4H), 2.14-2.07 (m,1H), 1.92-1.85 (m, 1H), 1.79-1.57 (m, 3H), 1.16 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 541 [M + H]⁺. 671

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47-7.23 (m, 2H), 7.17 (s, 1H), 7.07(s, 1H), 4.79-4.66 (m, 1H), 4.36-4.12 (m, 1H), 3.76 (s, 3H), 3.71 (s,3H), 3.55-3.39 (m, 1H), 3.26-3.16 (m, 1H), 3.14-2.98 (m, 1H), 2.98-2.83(m, 2H), 2.43-2.18 (m, 4H), 2.18-2.04 (m, 2H), 1.89-1.77 (m, 1H),1.77-1.60 (m, 2H), 1.60-1.50 (m, 1H), 1.47 (d, J = 6.8 Hz, 3H),1.19-1.03 (m, 4H). LCMS (ES, m/z): 494 [M + H]⁺ 672

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.61 (s, 1H), 7.48 (d, J = 9.2 Hz, 1H),7.44-7.33 (m, 2H), 4.90-4.92 (m, 1H), 4.80-4.70 (m, 1H), 4.33-4.21 (m,1H), 4.20-4.11 (m, 1H), 3.78 (s, 3H), 3.64-3.53 (m, 1H), 3.25-3.11 (m,1H), 2.99-2.79 (m, 2H), 2.39-2.14 (m, 5H), 1.80-1.59 (m, 3H), 1.53-1.41(m, 2H), 1.14 (d, J = 6.8 Hz, 3H), 1.06-0.94 (m, 4H). LCMS (ES, m/z):492 [M + H]⁺. 673

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.50-7.38 (m, 2H), 7.17-7.03 (m, 3H),4.85-4.72 (m, 1H), 4.65-4.50 (m, 1H), 4.12-4.00 (m, 1H), 3.85 (s, 3H),3.80 (s, 3H), 3.15-2.75 (m, 2H), 2.55-1.70 (m, 9H), 1.60-1.25 (m, 2H),1.17 (d, J = 6.6 Hz, 3H), 1.11-1.08 (m, 4H), 0.92 (d, J = 6.6 Hz, 3H).LCMS (ES, m/z): 552 [M + H]⁺ 674

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.61 (d, J = 8.8 Hz, 1H), 7.48 (d, J =9.2 Hz, 1H), 5.13-5.11 (m, 1H), 5.11-5.03 (m, 1H), 4.80-4.76 (m, 1H),3.79 (s, 3H), 3.24-2.88 (m, 3H), 2.56 2.18 (m, 5H), 2.12-1.94 (m, 4H),1.90-1.69 (m, 7H), 1.55-1.52 (m, 2H), 1.33-1.26 (m, 3H), 1.15 (d, J =6.4 Hz, 3H). LCMS (ES, m/z): 484 [M + H]⁺. 675

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.50-7.30 (m, 2H), 7.27-7.17 (m, 2H),7.07-6.92 (m, 2H), 4.77-4.54 (m, 2H), 4.41-4.15 (m, 2H), 3.74 (s, 3H),3.23-3.07 (m, 1H), 2.98-2.84 (m, 2H), 2.37-2.04 (m, 5H), 1.79-1.55 (m,3H), 1.30-1.16 (m, 2H), 1.11 (d, J = 6.9 Hz, 3H). LCMS (ES, m/z): 480[M + H]⁺ 676

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.84-7.71 (m, 2H), 7.59-7.50 (m, 4H),6.95-6.57 (m, 1H), 4.88-4.72 (m, 2H), 4.4-4.36 (m, 1H), 4.13-3.92 (m,3H), 3.76 (s, 3H), 3.62-3.44 (m, 3H), 3.11-2.85 (m, 2H), 2.61-2.43 (m,1H), 2.30-2.11 (m, 2H), 2.07-1.78 (m, 3H), 1.14 (d, J = 6.6 Hz, 3H).LCMS (ES, m/z): 528 [M + H]⁺. 677

LCMS (ES, m/z): 508 [M + H]⁺ 678

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.73-7.61 (m, 3H), 7.26-7.09 (m, 2H),6.31 (s, 1H), 5.00-4.81 (m, 2H), 3.82 (s, 3H), 3.70-3.68 (m, 1H),3.13-2.94 (m, 3H), 2.47-2.14 (m, 5H), 1.91-1.64 (m, 3H), 1.49-1.25 (m,2H), 1.17 (d, J = 6.4 Hz, 3H), 0.59-0.55 (m, 2H), 0.12-0.02 (m, 2H).LCMS (ES, m/z): 552 [M + H]⁺. 679

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52 (d, J = 9.2 Hz, 1H), 7.38 (d, J =9.2 Hz, 1H), 4.83-4.69 (m, 2H), 3.98-3.87 (m, 2H), 3.83-3.69 (m, 4H),3.23-3.12 (m, 1H), 3.11-3.03 (m, 2H), 3.00-2.99 (m, 1H), 2.95-2.85 (m,1H), 2.48-2.33 (m, 2H), 2.33-2.17 (m, 3H), 2.16-2.04 (m, 2H), 2.03-1.84(m, 5H), 1.80-1.53 (m, 4H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):470 [M + H]⁺. 680

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.93 (d, J = 8.7 Hz, 2H), 7.45-7.31 (m,3H), 7.27-7.14 (m, 3H), 7.13-7.01 (m, 2H), 6.87 (d, J = 90. Hz, 1H),4.81-4.75 (m, 1H), 4.37-4.18 (m, 1H), 3.75 (s, 3H), 3.62-3.44 (m, 1H),3.25-3.10 (m, 2H), 3.04-2.86 (m, 1H), 2.37-2.15 (m, 1H), 1.81-1.63 (m,1H), 1.12 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 495 [M + H]⁺ 681

LCMS (ES, m/z): 502 [M + H]⁺ 682

¹H-NMR (DMSO, 400 MHz) δ (ppm): 7.48-7.45 (m, 1H), 7.31-7.24 (m, 3H),6.89-6.86 (m, 2H), 6.21-6.16 (m, 1H), 5.97-5.96 (m, 1H), 4.83-4.75 (m,1H), 4.68-4.63 (m, 1H), 3.72 (s, 3H), 3.67 (s, 3H), 3.13-3.06 (m, 1H),2.89-2.81 (m, 2H), 2.27-2.11 (m, 2H), 2.07-1.87 (m, 3H), 1.68-1.57 (m,3H), 1.36-1.24 (m, 2H), 1.07 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 508[M + H]⁺. 683

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.91-7.82 (m, 2H), 5.09-5.05 (m, 1H),4.35-4.29 (m, 1H), 4.90-4.07 (m, 1H), 3.82 (s, 3H), 3.61-3.58 (m, 1H),3.53-3.47 (m, 1H), 3.41-3.36 (m, 2H), 3.15-3.04 (m, 3H), 2.57-2.54 (m,1H), 2.46-2.40 (m, 2H), 2.37-2.20 (m, 4H), 2.04-2.01 (m, 2H), 1.92-1.89(m, 3H), 1.81-1.78 (m, 3H), 1.70-1.59 (m, 4H) 1.17 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 511 [M + H]⁺ 684

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53 (d, J = 9.0 Hz, 1H), 7.44 (d, J =9.0 Hz, 1H), 7.32-7.18 (m, 3H), 7.17-7.10 (m, 1H), 5.39-5.23 (m, 1H),4.80-4.67 (m, 2H), 4.66-4.58 (m, 3H), 4.56-4.46 (m, 1H), 3.88-3.64 (m,4H), 3.26-3.13 (m, 1H), 3.03-2.92 (m, 1H), 2.91-2.84 (m, 1H), 2.48-2.34(m, 1H), 2.33-2.09 (m, 4H), 1.82-1.60 (m, 4H), 1.58-1.44 (m, 1H),1.23-1.10 (m, 3H). LCMS (ES, m/z): 531 [M + H]⁺. 685

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56-7.54 (m, 1H), 7.45-7.41 (m, 1H),5.18-5.16 (m, 1H), 5.02-4.96 (m, 1H), 4.77-4.74 (m, 1H), 3.79 (s, 3H),3.42-3.40 (m, 1H), 3.21-3.18 (m, 1H), 2.92-2.88 (m, 1H), 2.62-2.58 (m,1H), 2.53-2.39 (m, 2H), 2.31-2.25 (m, 3H), 2.07-1.96 (m, 3H), 1.81-1.69(m, 5H), 1.62 (d, J = 8.0 Hz, 3H), 1.54-1.50 (m, 1H), 1.40-1.32 (m, 2H),1.33-1.23 (m, 4H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 498 [M +H]⁺. 686

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46-7.32 (m, 4H), 4.84-4.71 (m, 1H),4.70-4.55 (m, 2H), 4.55-4.44 (m, 1H), 4.05-3.91 (m, 1H), 3.79 (s, 3H),3.52-3.36 (m, 3H), 3.30-3.16 (m, 2H), 3.04-2.91 (m, 1H), 2.70-2.60 (m,1H), 2.51-2.37 (m, 1H), 2.34-2.04 (m, 3H), 2.03-1.86 (m, 1H), 1.82-1.67(m, 1H), 1.65-1.51 (m, 1H), 1.47 (d, J = 7.2 Hz, 3H), 1.14 (d, J = 6.8Hz, 3H). LCMS (ES, m/z): 485 [M + H]⁺. 687

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 9.45 (s, 1H), 8.12 (s, 1H), 7.56 (d, J= 9.2 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H), 4.84-4.74 (m, 4H), 3.79 (s,3H), 3.33-3.25 (m, 1H), 3.03-2.96 (m, 2H), 2.46-2.12 (m, 5H), 1.88-1.62(m, 4H), 1.55-1.41 (m, 1H), 1.16 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):532 [M + H]⁺. 688

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56 (d, J = 8.0 Hz, 1H), 7.45 (d, J =8.8 Hz, 1H), 5.20-5.16 (m, 1H), 4.84-4.79 (m, 1H), 4.76-4.73 (m, 2H),3.79 (s, 3H), 3.37-3.36 (m, 2H), 3.24-3.16 (m, 1H), 2.96-2.92 (m, 2H),2.61-2.49 (m, 2H), 2.38-2.23 (m, 5H), 1.91-1.82 (m, 2H), 1.80-1.56 (m,5H), 1.15 (d, J = 6.4 Hz, 3H), 0.47-0.41 (m, 4H). LCMS (ES, m/z): 509[M + H]⁺. 689

LCMS (ES, m/z): 508 [M + H]⁺ 690

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51-7.39 (m, 2H), 7.39-7.31 (m, 2H),7.31-7.21 (m, 2H), 7.21-7.07 (m, 1H), 4.87 (s, 2H), 4.64-4.46 (m, 2H),3.77 (s, 3H), 3.19-3.03 (m, 1H), 2.96-2.82 (m, 1H), 2.81-2.63 (m, 1H),2.43-2.18 (m, 5H), 2.09-1.94 (m, 1H), 1.91-1.77 (m, 1H), 1.68-1.59 (m,3H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 477 [M + H]⁺ 691

LCMS (ES, m/z): 511 [M + H]⁺ 692

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.60-7.51 (d, J = 8.8 Hz, 1H),7.50-7.37 (d, J = 8.8 Hz, 1H), 4.87-4.69 (m, 3H), 4.65-4.48 (m, 1H),3.79 (s, 3H), 3.58-3.48 (m, 1H), 3.23-3.07 (m, 1H), 3.00-2.88 (m, 1H),2.56-2.48 (m, 1H), 2.47-2.32 (m, 2H), 2.32-2.16 (m, 3H), 2.12-1.88 (m,4H), 1.81-1.61 (m, 5H), 1.59-1.48 (m, 1H), 1.46-1.23 (m, 5H), 1.21-1.03(d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 484 [M + H]⁺. 693

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.10 (s, 1H), 7.99 (s, 1H), 7.54 (d, J= 8.8 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 5.21-5.19 (m, 1H), 4.86-4.72(m, 2H), 4.51-4.39 (m, 2H), 3.79 (s, 3H), 3.25-3.18 (m, 1H), 3.01-2.94(m, 2H), 2.43-2.19 (m, 5H), 1.85-1.74 (m, 3H), 1.60 (m, 1H), 1.43 (m,1H), 1.24-1.18 (m, 6H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 522[M + H]⁺ 694

LCMS (ES, m/z): 477 [M + H]⁺ 695

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.93-7.83 (m, 2H), 7.81-7.73 (m, 1H),7.19 (d, J = 7.6 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 5.01 (s, 2H),4.83-4.69 (m, 2H), 3.83 (s, 4H), 3.13-2.95 (m, 3H), 2.43-2.17 (m, 5H),1.97-1.87 (m, 1H), 1.87-1.68 (m, 3H), 1.46-1.35 (m, 1H), 1.17 (d, J =6.4 Hz, 3H), 0.58-0.38 (m, 4H). LCMS (ES, m/z): 519 [M + H]⁺. 696

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.54-7.43 (m, 2H), 5.15-5.05 (m, 1H),4.89-4.74 (m, 3H), 3.79 (s, 3H), 3.42-3.32 (m, 2H), 3.19-3.15 (m, 1H),2.96-2.90 (m, 2H), 2.46-2.18 (m, 7H), 1.95-1.80 (m, 2H), 1.79-1.63 (m,5H), 1.15 (d J = 6.8 Hz, 3H), 1.07 (s, 3H), 1.03 (s, 3H). LCMS (ES,m/z): 511 [M + H]⁺ 697

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.41-8.35 (m, 2H), 7.60-7.58 (m, 1H),7.53 (d, J = 8.8 Hz, 1H), 7.43 (d, J = 9.2 Hz, 1H), 7.18-6.73 (m, 1H),4.86-4.70 (m, 2H), 4.56-4.41 (m, 2H), 3.79 (s, 3H), 3.27-3.13 (m, 1H),3.04-2.90 (m, 2H), 2.42-2.09 (m, 5H), 1.86-1.62 (m, 3H), 1.56-1.29 (m,2H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 529 [M + H]⁺. 698

¹H-NMR (DMSO, 300 MHz) δ (ppm): 12.46 (br, 1H), 8.08-7.93 (m, 1H),7.87-7.59 (m, 3H), 7.37-7.03 (m, 6H), 6.87 (d, J = 9.0 Hz, 1H),4.70-4.51 (m, 1H), 4.38-4.17 (m, 1H), 3.62 (s, 3H), 3.49-3.37 (m, 1H),3.17-2.93 (m, 2H), 2.93-2.75 (m, 1H), 2.22-2.04 (m, 1H), 1.76-1.48 (m,1H), 1.04 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 495 [M + H]⁺ 699

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53 (d, J = 9.2 Hz, 1H), 7.42 (d, J =9.2 Hz, 1H), 5.28-5.12 (m, 1H), 4.80-4.65 (m, 2H), 3.79 (s, 3H),3.23-3.15 (m, 1H), 3.03-2.96 (m, 1H), 2.93-2.82 (m, 1H), 2.58-2.25 (m,7H), 2.05-1.81 (m, 5H), 1.79-1.52 (m, 4H), 1.48-1.22 (m, 2H), 1.14 (d, J= 6.4 Hz, 3H), 1.13-1.09 (m 1H). LCMS (ES, m/z): 520 [M + H]⁺. 700

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56-7.37 (m, 2H), 7.27-7.08 (m, 4H),4.82-4.64 (m, 2H), 4.30-4.23 (m, 1H), 4.12-3.92 (m, 2H), 3.90-3.76 (m,4H), 3.72-3.60 (m, 1H), 3.23-3.07 (m, 3H), 2.99-2.75 (m, 2H), 2.71-2.59(m, 1H), 2.37-2.16 (m, 4H), 1.78-1.70 (m, 1H), 1.14 (d, J = 6.0 Hz, 3H).LCMS (ES, m/z): 528 [M + H]⁺. 701

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.62-7.42 (m, 2H), 7.42-7.33 (m, 1H),7.32-7.16 (m, 1H), 7.06-6.87 (m, 1H), 6.57 (s, 1H), 5.85-5.60 (m, 1H),5.36-5.14 (m, 1H), 4.83-4.67 (m, 3H), 4.41-4.19 (m, 1H), 3.79 (s, 3H),3.31-3.16 (m, 1H), 3.04-2.95 (m, 2H), 2.57-2.41 (m, 1H), 2.41-2.20 (m,2H), 2.13-1.91 (m, 2H), 1.90-1.72 (m, 1H), 1.63-1.39 (m, 2H), 1.31-1.11(m, 4H), 1.06-0.79 (m, 1H). LCMS (ES, m/z): 520 [M + H]⁺ 702

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.91-7.90 (m, 2H), 5.07-5.00 (m, 3H),4.96-4.87 (m, 1H), 3.83 (s, 3H), 3.68-3.66 (m, 1H), 3.09-3.02 (m, 2H),2.47-2.41 (m, 3H), 2.28-2.41 (m, 2H), 2.08-1.90 (m, 5H), 1.89-1.78 (m,3H), 1.74-1.33 (m, 8H), 1.17 (d, J = 6.8, 3H). LCMS (ES, m/z): 484 [M +H]⁺. 703

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.90 (s, 1H), 7.52 (s, 1H), 7.27-7.21(m, 2H), 4.91-4.87 (m, 2H), 4.74-4.69 (m, 1H), 4.63-4.60 (m, 2H),4.20-4.14 (m, 1H), 3.77 (s, 3H), 3.15-3.07 (m, 1H), 2.82-2.75 (m, 1H),2.38-2.28 (m, 1H), 2.26-2.21 (m, 1H), 2.15-1.98 (m, 4H), 1.82-1.75 (m,2H), 1.68-1.58 (m, 3H), 1.13 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 516[M + H]⁺ 704

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.27 (s, 1H), 7.80 (s, 1H), 7.58 (d, J= 8.8 Hz, 1H), 7.48 (d, J = 8.8 Hz, 1H), 4.79-4.76 (m, 2H), 3.80 (s,3H), 3.33-2.90 (m, 3H), 2.48-2.00 (m, 8H), 1.99-1.37 (m, 9H), 1.17 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 504 [M + H]⁺ 705

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52 (d, J = 9.2 Hz, 1H), 7.39 (d, J =8.8 Hz, 1H), 4.82-4.69 (m, 2H), 4.07-3.94 (m, 1H), 3.93-3.84 (m, 1H),3.83-3.70 (m, 4H), 3.23-3.08 (m, 2H), 3.07-2.97 (m, 2H), 2.95-2.85 (m,1H), 2.51-2.34 (m, 2H), 2.33-2.19 (m, 3H), 2.15-2.02 (m, 2H), 2.01-1.84(m, 5H), 1.81-1.55 (m, 4H), 1.14 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z):470 [M + H]⁺. 706

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.82 (d, J = 7.6 Hz, 1H), 7.62-7.40 (m,4H), 7.26 (d, J = 8.0 Hz, 1H), 4.80-4.70 (m, 1H), 4.65 (s, 2H),4.30-4.10 (m, 1H), 3.75 (s, 3H), 3.25-3.10 (m, 1H), 2.98-2.85 (m, 1H),2.45-2.00 (m, 6H), 1.75-1.40 (m, 5H), 1.13 (d, J = 6.4 Hz, 3H). LCMS(ES, m/z): 487 [M + H]⁺. 707

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.75-7.63 (m, 2H), 7.63-7.37 (m, 4H),4.84-4.69 (m, 1H), 4.49 (s, 2H), 4.32-4.18 (m, 1H), 3.79 (s, 3H),3.29-3.12 (m, 1H), 3.04-2.91 (m, 1H), 2.51-2.36 (m, 1H), 2.34-2.16 (m,3H), 2.15-2.00 (m, 2H), 1.85-1.69 (m, 1H), 1.63-1.41 (m, 4H), 1.16 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 487 [M + H]⁺. 708

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47-7.28 (m, 7H), 6.25 (s, 1H),4.84-4.74 (m, 1H), 4.68-4.54 (m, 1H), 3.79 (s, 3H), 3.33-3.18 (m, 1H),3.03-2.96 (m, 1H), 2.46-2.12 (m, 4H), 2.05-1.72 (m, 4H), 1.59-1.45 (m,1H), 1.16 (d, J = 6.6 Hz, 3H), 1.14-1.02 (m, 1H), 0.99-0.87 (m, 1H).LCMS (ES, m/z): 478 [M + H]⁺. 709

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.59-7.40 (m, 4H), 5.60-5.40 (m, 1H),4.92-4.42 (m, 3H), 4.02-3.88 (m, 1H), 3.75-3.35 (m, 6H), 3.32-3.15 (m,2H), 3.30-2.91 (m, 2H), 2.32-2.24 (m, 2H), 1.73-1.68 (m, 1H), 1.40 (d, J= 6.9 Hz, 3H), 1.12 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 506 [M + H]⁺.710

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.57-7.44 (m, 3H), 7.37 (d, J = 8.8 Hz,1H), 6.27-6.25 (m, 1H), 4.81-4.67 (m, 1H), 4.48-4.38 (m, 3H), 3.77 (s,3H), 3.22-3.07 (m, 1H), 2.98-2.81 (m, 1H), 2.46-2.17 (m, 4H), 2.12-2.08(m, 2H), 1.83-1.50 (m, 5H), 1.49-1.37 (m, 2H), 1.26-1.17 (m, 2H), 1.12(d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 492 [M + H]⁺. 711

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.77-7.56 (m, 1H), 7.47-7.45 (m, 1H),4.91-4.82 (m, 2H), 4.79-4.65 (m, 1H), 4.18-4.09 (m, 1H), 3.79 (s, 3H),3.20-3.14 (m, 1H), 2.99-2.92 (m, 2H), 2.47-2.26 (m, 5H), 1.98-1.45 (m,14H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 470 [M + H]⁺. 712

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.63-7.49 (m, 1H), 7.46-7.28 (m, 1H),5.32-5.11 (m, 1H), 5.11-4.97 (m, 1H), 4.82-4.63 (m, 1H), 3.78 (s, 3H),3.28-3.17 (m, 1H), 3.06-2.88 (m, 2H), 2.63-2.32 (m, 2H), 2.32-2.18 (m,3H), 2.11-1.89 (m, 8H), 1.84-1.66 (m, 6H), 1.49-1.33 (m, 2H), 1.15 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 534 [M + H]⁺. 713

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.98-7.78 (m, 2H), 5.14-5.12 (m, 1H),4.01-3.88 (m, 2H), 3.88-3.69 (m, 4H), 3.50-3.38 (m, 2H), 3.30-3.20 (m,1H), 3.21-3.06 (m, 2H), 3.06-2.93 (m, 1H), 2.67-2.40 (m, 2H), 2.40-2.18(m, 3H), 2.12-1.93 (m, 3H), 1.93-1.73 (m, 4H), 1.67-1.61 (m, 3H), 1.56(d, J = 6.8 Hz, 3H), 1.50-1.29 (m, 2H), 1.18 (d, J = 6.8 Hz, 3H). LCMS(ES, m/z): 498 [M + H]⁺. 714

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.61-7.30 (m, 4H), 5.76-5.53 (m, 2H),4.83-4.69 (m, 1H), 4.53-4.30 (m, 1H), 3.79 (s, 3H), 3.27-3.13 (m, 1H),3.04-2.93 (m, 1H), 2.93-2.78 (m, 1H), 2.59-2.38 (m, 1H), 2.31-1.99 (m,5H), 1.87-1.71 (m, 1H), 1.71-1.47 (m, 4H), 1.20 (d, J = 6.8 Hz, 6H),1.15 (d, J = 6.8 Hz, 6H). .LCMS (ES, m/z): 494 [M + H]⁺ 715

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.01-7.95 (m, 2H), 7.59-7.52 (m, 3H),7.49-7.43 (m, 1H), 7.38-7.31 (m, 1H), 4.92-4.83 (m, 1H), 4.79-4.71 (m,1H), 3.79 (s, 3H), 3.03-2.96 (m, 1H), 2.90-2.82 (m, 1H), 2.79-2.71 (m,1H), 2.45-2.39 (m, 1H), 2.38-2.21 (m, 4H), 1.89-1.72 (m, 3H), 1.64-1.52(m, 2H), 1.16 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 527 [M + H]⁺. 716

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.17 (s, 1H), 8.09 (s, 1H), 7.54 (d, J= 9.2 Hz, 1H), 7.42 (d, J = 9.2 Hz, 1) 4.88-4.54 (m, 3H), 4.23-4.21 (m,1H), 3.78 (s, 3H), 3.19-2.92 (m, 3H), 2.39-2.10 (m, 6H), 1.81-1.69 (m,4H), 1.45-1.42 (m, 1H), 1.15 (d, J = 6.4 Hz, 3H), 6.70-0.67 (m, 4H).LCMS (ES, m/z): 520 [M + H]⁺ 717

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.52-7.28 (m, 7H), 6.57 (s, 1H),4.81-4.67 (m, 1H), 4.36-4.19 (m, 1H), 3.79 (s, 3H), 3.30-3.21 (m, 1H),3.04-2.88 (m, 1H), 2.50-1.88 (m, 10H), 1.82-1.57 (m, 2H), 1.38-1.24 (m,1H), 1.22-1.01 (m, 4H). LCMS (ES, m/z): 519 [M + H]⁺ 718

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.51-7.41 (m, 2H), 7.17-7.03 (m, 4H),4.77-4.69 (m, 2H), 4.43-4.29 (m, 2H), 3.76 (s, 3H), 3.21-3.14 (m, 1H),2.99-2.92 (m, 2H), 2.43-2.03 (m, 8H), 1.77-1.57 (m, 3H), 1.28-1.12 (m,5H). LCMS (ES, m/z): 476 [M + H]⁺. 719

LCMS (ES, m/z): 493 [M + H]⁺ 720

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.50-7.42 (d, J = 9.2 Hz, 1H),7.36-7.26 (d, J = 8.8 Hz, 1H), 7.24-7.13 (m, 1H), 7.16-7.01 (m, 2H),5.01-4.89 (m, 1H), 4.77-4.66 (m, 1H), 3.76 (s, 3H), 3.71-3.54 (m, 1H),3.42-3.51 (m, 1H), 3.22-3.10 (m, 1H), 3.04-2.75 (m, 3H), 2.45-2.21 (m,4H), 2.15-1.96 (m, 1H), 1.95-1.78 (m, 2H), 1.78-1.62 (m, 3H), 1.34 (d, J= 6.8 Hz, 3H), 1.13 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 526 [M + H]⁺.721

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52 (d, J = 9.2 Hz, 1H), 7.39 (d, J =9.2 Hz, 1H), 4.82-4.69 (m, 2H), 4.02-3.91 (m, 1H), 3.78 (s, 3H),3.51-3.39 (m, 1H), 3.24-3.14 (m, 1H), 3.13-3.01 (m, 2H), 3.01-2.98 (m,1H), 2.94-2.84 (m, 1H), 2.52-2.34 (m, 2H), 2.34-2.17 (m, 3H), 2.10-1.82(m, 5H), 1.79-1.63 (m, 4H), 1.62-1.45 (m, 3H), 1.43-1.25 (m, 2H), 1.14(d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 484 [M + H]⁺. 722

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.62-7.39 (m, 2H), 7.23-7.11 (m, 1H),6.95-6.23 (m, 3H), 4.83-4.71 (m, 1H), 4.45-3.98 (m, 1H), 3.85-3.63 (m,4H), 3.33-3.15 (m, 1H), 2.93-2.75 (m, 2H), 2.61-2.12 (m, 5H), 2.10-1.55(m, 6H), 1.41-1.30 (m, 4H), 1.25-1.12 (m, 3H). LCMS (ES, m/z): 531 [M +H]⁺. 723

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.49-7.34 (m, 2H), 4.88-4.72 (m, 2H),3.76 (s, 3H), 3.32-3.00 (m, 5H), 2.93-2.86 (m, 4H), 2.42-2.06 (m, 7H),1.89-1.66 (m, 8H), 1.32-1.11 (m, 7H). LCMS (ES, m/z): 498 [M + H]⁺. 724

¹H NMR (400 MHz, CD₃OD) δ (ppm): 7.60 (d, J = 9.2 Hz, 1H), 7.43 (d, J =8.8 Hz, 1H), 5.19-5.17 (m, 1H), 4.96-4.93 (m, 1H), 4.88-4.76 (m, 1H),3.96-3.93 (m, 1H), 3.89-3.87 (m, 1H), 3.79 (s, 3H), 3.64-3.62 (m, 1H),3.47-3.38 (m, 2H), 3.16-3.14 (m, 1H), 2.94-2.90 (m, 1H), 2.54-2.41 (m,3H), 2.27-2.24 (m, 3H), 2.06-1.97 (m, 3H), 1.81-1.76 (m, 1H), 1.74-1.55(m, 8H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 500 [M + H]⁺ 725

¹H-NMR (DMSO, 400 MHz) δ (ppm): 7.66-7.21 (m, 7H), 6.11-5.79 (m, 1H),4.74-4.57 (m, 1H), 4.55-4.24 (m, 1H), 3.67 (d, J = 5.7 Hz, 3H),3.21-3.00 (m, 1H), 2.97-2.82 (m, 1H), 2.65 (s, 1H), 2.45 (s, 2H),2.39-2.09 (m, 3H), 2.09-1.89 (m, 3H), 1.87-1.73 (m, 1H), 1.73-1.40 (m,2H), 1.31-1.18 (m, 1H), 1.09 (d, J = 6.4 Hz, 3H), 0.89-0.73 (m, 1H).LCMS (ES, m/z): 524 [M + H]⁺. 726

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53 (d, J = 8.8 Hz, 1H), 7.37 (d, J =8.8 Hz, 1H), 4.81-4.75 (m, 2H), 3.78 (s, 3H), 3.18-3.15 (m, 1H),3.08-3.06 (m, 1H), 2.97-2.89 (m, 4H), 2.42-2.32 (m, 2H), 2.31-2.24 (m,3H), 2.03-1.88 (m, 6H), 1.85-1.80 (m, 1H), 1.75-1.70 (m, 5H), 1.51-1.47(m, 2H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 493 [M + H]⁺. 727

LCMS (ES, m/z): 508 [M + H]⁺ 728

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.47-7.19 (m, 5H), 7.17-7.14 (m, 1H),4.74-4.47 (m, 2H), 4.18-3.97 (m, 4H), 3.75-3.45 (m, 5H), 3.42-3.28 (m,2H), 2.89-2.84 (m, 1H), 2.21-2.20 (m, 2H), 1.76-1.67 (m, 3H), 1.45-1.35(m, 1H), 1.12 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 496 [M + H]⁺. 729

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.52 (d, J = 9.0 Hz, 1H), 7.38 (d, J =9.0 Hz, 1H), 4.83-4.67 (m, 1H), 4.44-4.29 (m, 1H), 3.78 (s, 3H),3.52-3.43 (m, 1H), 3.25-3.11 (m, 1H), 2.98-2.83 (m, 3H), 2.55-2.37 (m,3H), 2.33-2.15 (m, 4H), 2.05-1.84 (m, 5H), 1.81-1.62 (m, 4H), 1.60-1.36(m, 7H), 1.14 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 498 [M + H]⁺. 730

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.85 (s, 1H), 7.55 (d, J = 8.8 Hz, 1H),7.49-7.39 (m, 2H), 5.45-5.35 (m, 1H), 5.06-4.93 (m, 1H), 4.85-4.67 (m,3H), 3.79 (s, 3H), 3.29-3.17 (m, 1H), 3.00-2.89 (m, 2H), 2.49-2.16 (m,4H), 2.04-1.95 (m, 1H), 1.93-1.82 (m, 1H), 1.79-1.61 (m, 3H), 1.36-1.28(m, 1H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 516 [M + H]⁺. 731

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.46 (s, 1H), 8.05-8.01 (m, 1H),7.95-7.89 (m, 1H), 7.88-7.80 (m, 2H), 6.53 (s, 1H), 5..2-4.88 (m, 1H),4.85-4.80 (m, 1H), 3.83 (s, 3H), 3.18-2.95 (m, 3H), 2.53-2.10 (m, 5H),2.02-1.62 (m, 4H), 1.59-1.45 (m, 1H), 1.18 (d, J = 6.8 Hz, 3H). LCMS(ES, m/z): 513 [M + H]⁺. 732

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.54-7.48 (m, 1H), 7.42-7.35 (m, 1H),4.80-4.67 (m, 1H), 4.50-4.45 (m, 1H), 4.41-4.31 (m, 1H), 3.78 (s, 3H),3.75-3.56 (m, 2H), 3.56-3.40 (m, 2H), 3.30-3.19 (m, 1H), 3.01-2.97-2.86(m, 2H), 2.56-2.44 (m, 1H), 2.34-2.21 (m, 4H), 2.13-2.00 (m, 2H),1.97-1.83 (m, 4H), 1.82-1.62 (m, 5H), 1.56-1.42 (m, 1H), 1.14 (d, J =6.8 Hz, 3H). LCMS (ES, m/z): 497 [M + H]⁺. 733

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.86-7.81 (m, 2H), 7.68 (s, 1H), 7.38(s, 1H), 5.96-5.82 (m, 2H), 4.90-4.82 (m, 1H), 4.70-4.57 (m, 1H), 3.82(s, 3H), 3.19-3.07 (m, 1H), 3.07-2.96 (m, 1H), 2.61-2.51 (m, 1H),2.40-2.14 (m, 5H), 1.97-1.85 (m, 1H), 1.82-1.72 (m, 2H), 1.71-1.53 (m,3H), 1.17 (d, J = 6.4 Hz, 3H), 0.94-0.82 (m, 2H), 0.57-0.49 (m, 2H).LCMS (ES, m/z): 492 [M + H]⁺. 734

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.40-7.20 (m, 2H), 7.18-7.05 (m, 3H),7.10-6.98 (m, 2H), 4.79-4.66 (m, 1H), 4.37-4.33 (m, 1H), 3.77 (s, 3H),3.64-3.51 (m, 1H), 3.29-3.02 (m, 4H), 3.02-2.78 (m, 3H), 2.70-2.58 (m,1H), 2.49-2.32 (m, 1H), 2.32-2.14 (m, 2H), 1.98-1.62 (m, 4H), 1.53 (d, J= 6.8 Hz, 3H), 1.12 (d, J = 6.4 Hz, 3H), 0.79-0.75 (m, 1H). LCMS (ES,m/z): 461 [M + H]⁺. 735

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47-7.28 (m, 7H), 6.25 (s, 1H),4.84-4.74 (m, 1H), 4.68-4.54 (m, 1H), 3.79 (s, 3H), 3.33-3.18 (m, 1H),3.08-2.96 (m, 1H), 2.46-1.72 (m, 8H), 1.59-1.45 (m, 1H), 1.16 (d, J =6.6 Hz, 3H), 1.14-1.05 (m, 1H), 1.01-0.87 (m, 1H). LCMS (ES, m/z): 478[M + H]⁺. 736

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53 (s, 1H), 7.51-7.40 (m, 3H),5.08-4.94 (m, 1H), 4.82-4.71 (m, 1H), 4.66-4.52 (m, 1H), 4.52-4.38 (m,1H), 3.99-3.85 (m, 1H), 3.79 (s, 3H), 3.43-3.36 (m, 4H), 3.29-3.14 (m,1H), 3.08-2.89 (m, 3H), 2.72-2.54 (m, 1H), 2.54-2.38 (m, 1H), 2.38-2.21(m, 3H), 1.83-1.67 (m, 1H), 1.43 (d, J = 6.9 Hz, 3H), 1.16 (d, J = 6.6Hz, 3H). LCMS (ES, m/z): 497 [M + H]⁺. 737

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.82 (s, 1H), 7.54-7.43 (m, 3H),5.73-5.63 (m, 2H), 4.78-4.75 (m, 1H), 4.59-4.55 (m, 1H), 3.76 (s, 3H),3.18-3.13 (m, 1H), 2.99-2.93 (m, 1H), 2.51-2.45 (m, 1H), 2.32-2.20 (m,3H), 2.13-2.09 (m, 2H), 1.77-1.71 (m, 2H), 1.67-1.58 (m, 3H), 1.12 (d, J= 6.4 Hz, 3H). LCMS (ES, m/z): 486 [M + H]⁺. 738

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.48 (s, 1H), 8.41 (s, 1H), 7.53-7.38(m, 2H), 4.77-4.55 (m, 4H), 3.75 (s, 3H), 3.25-2.85 (m, 3H), 2.50 (s,3H), 2.40-2.15 (m, 5H), 1.80-1.45 (m, 5H), 1.13 (d, J = 6.6 Hz, 3H).LCMS (ES, m/z): 478 [M + H]⁺. 739

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.57 (d, J = 8.8 Hz, 1H), 7.47 (d, J =9.2 Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.32-7.22 (m, 1H), 7.06-7.02 (m,2H), 5.18-5.05 (m, 1H), 5.02-4.91 (m, 2H), 4.82-4.68 (m, 2H), 4.56-4.43(m, 1H), 3.79 (s, 3H), 3.28-3.16 (m, 1H), 3.05-2.86 (m, 2H), 2.56-2.41(m, 1H), 2.38-2.14 (m, 4H), 2.03-1.88 (m, 1H), 1.86-1.72 (m, 2H),1.68-1.65 (m, 2H), 1.16 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 553 [M +H]⁺. 740

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.49-7.30 (m, 2H), 6.97-6.84 (m, 2H),6.82-6.69 (m, 1H), 4.80-4.68 (m, 1H), 4.37-4.24 (m, 3H), 3.82-3.71 (m,9H), 3.27-3.11 (m, 1H), 3.02-2.86 (m, 1H), 2.50-2.31 (m, 1H), 2.31-2.12(m, 3H), 2.12-1.97 (m, 2H), 1.81-1.66 (m, 1H), 1.60-1.31 (m, 4H), 1.14(d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 522 [M + H]⁺ 741

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.57 (d, J = 9.0 Hz, 1H), 7.46 (d, J =9.0 Hz, 1H), 5.01-4.89 (m, 2H), 4.83-4.67 (m, 2H), 4.03-3.85 (m, 2H),3.84-3.68 (m, 4H), 3.58-3.43 (m, 2H), 3.27-3.09 (m, 1H), 3.06-2.89 (m,2H), 2.56-2.15 (m, 5H), 2.09-1.86 (m 4H), 1.82-1.49 (m 5H), 1.14 (d, J =6.6 Hz, 3H). LCMS (ES, m/z): 486 [M + H]⁺. 742

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.42 (d, J = 8.8 Hz, 1H), 7.32 (d, J =8.8 Hz, 1H), 7.29-7.27 (m, 1H), 7.27-7.22 (s, 1H), 4.73-4.70 (m, 2H),3.76 (s, 3H), 3.72 (s, 3H), 3.55-3.53 (m, 1H), 3.30-3.21 (m, 1H),3.05-3.02 (m, 1H), 3.00-2.86 (m, 2H), 2.86-2.77 (m, 1H), 2.29-2.19 (m,6H), 1.88-1.50 (m, 7H), 1.15-1.12 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):494 [M + H]+. 743

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.86 (d, J = 7.8 Hz, 1H), 7.53-7.47 (m,1H), 7.47-7.40 (m, 1H), 7.40-7.33 (m, 1H), 7.33-7.22 (m, 2H), 4.85-4.73(m, 2H), 4.13-4.04 (m, 2H), 3.79 (s, 3H), 3.74-3.66 (m, 2H), 3.43-3.35(m, 4H), 3.25-3.12 (m, 1H), 3.00-2.88 (m, 1H), 2.66-2.40 (m, 2H),2.30-2.20 (m, 1H), 1.86-1.51 (m, 3H), 1.14 (d, J = 6.8 Hz, 3H). LCMS(ES, m/z): 478 [M + H]⁺. 744

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.71 (d, J = 8.4 Hz, 2H), 7.49-7.40 (m,4H), 4.85-4.70 (m, 1H), 4.50 (s, 2H), 4.30-4.10 (m, 1H), 3.75 (s, 3H),3.25-3.10 (m, 1H), 3.00-2.90 (m, 1H), 2.45-2.00 (m, 6H), 1.75-1.35 (m,5H), 1.14 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 487 [M + H]⁺. 745

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.50 (s, 1H), 7.96-7.84 (m, 2H),5.05-4.95 (m, 2H), 4.87-4.77 (m, 2H), 3.83 (s, 3H), 3.14-2.94 (m, 3H),2.53 (s, 3H), 2.50-2.37 (m, 2H), 2.35-2.17 (m, 3H), 2.05-1.79 (m, 4H),1.60-1.39 (m, 1H), 1.23-1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 512[M + H]⁺. 746

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49-7.37 (m, 4H), 4.82-4.70 (m, 2H),4.60-4.40 (m, 2H), 3.88-3.80 (m, 1H), 3.75 (s, 3H), 3.25-3.15 (m, 1H),2.98-2.70 (m, 5H), 2.60-2.38 (m, 3H), 2.35-2.15 (m, 2H), 1.80-1.75 (m,5H), 1.40 (d, J = 6.8 Hz, 3H), 1.13 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):511 [M + H]⁺. 747

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56 (d, J = 8.8 Hz, 1H), 7.41 (d, J =8.8 Hz, 1H), 5.03-4.90 (m, 1H), 4.80-4.65 (m, 2H), 3.79 (s, 3H),3.23-3.15 (m, 1H), 3.03-2.96 (m, 1H), 2.93-2.82 (m, 1H), 2.45-2.32 (m,2H), 2.30-2.03 (m, 6H), 2.02-1.62 (m, 8H), 1.60-1.45 (m, 3H), 1.14 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 520 [M + H]⁺. 748

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.04-7.92 (m, 1H), 7.92-7.82 (m, 2H),7.73-7.59 (m, 1H), 7.48-7.33 (m, 1H), 7.28-7.12 (m, 1H), 5.85 (s, 2H),4.87-4.85 (m, 1H), 4.75-4.51 (m, 1H), 3.83 (s, 3H), 3.28-3.01 (m, 2H),2.43-2.19 (m, 3H), 2.19-2.07 (m, 2H), 2.07-1.97 (m, 2H), 1.97-1.88 (m,1H), 1.88-1.76 (m, 1H), 1.71-1.42 (m, 3H), 3 1.18 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 478 [M + H]⁺ 749

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.52-8.50 (m, 1H), 8.00-7.92 (m, 1H),7.90-7.62 (m, 3H), 7.60-7.31 (m, 1H), 4.852-4.76 (m, 2H), 3.83-3.72 (m,3H), 3.30-3.21 (m, 1H), 3.07 (m, 1H), 2.87-2.84 (m, 1H), 2.47-2.39 (m,1H), 2.35-2.28 (m, 4H), 2.18-2.02 (m, 2H), 2.00-1.85 (m, 2H), 1.85-1.67(m, 2H), 1.59-1.52 (m, 1H), 1.20-1.11 (m, 4H). LCMS (ES, m/z): 493 [M +H]⁺. 750

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.77-7.56 (m, 3H), 7.44 (s, 1H), 6.22(t, J = 2.4 Hz, 1H), 4.98-4.92 (m, 1H), 4.84-4.80 (m, 1H), 4.67-4.62 (m,2H), 4.13-4.01 (m, 1H), 3.99-3.89 (m, 1H), 3.79 (s, 3H), 3.50-3.30 (m,1H), 3.19-2.99 (m, 3H), 2.80-2.45 (m, 2H), 2.35-2.01 (m, 4H), 1.90-1.75(m, 1H), 1.57 (d, J = 7.2 Hz, 3) 1.13 (d, J = 6.8 Hz, 3H). LCMS (ES,m/z): 486 [M + H]⁺. 751

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.74 (d, J = 8.8 Hz, 1H), 7.56 (d, J =9.2 Hz, 1H), 7.47-7.38 (m, 1H), 7.35-7.20 (m, 2H), 5.25-5.16 (m, 1H),4.87-4.79 (m, 1H), 4.34-4.28 (m, 1H), 4.00-3.88 (m, 1H), 3.82 (s, 3H),3.63-3.47 (m, 1H), 3.13-3.03 (m, 1H), 3.03-2.88 (m, 1H), 2.40-2.16 (m,3H), 2.16-2.02 (m, 3H), 2.02-1.95 (m, 1H), 1.95-1.82 (m, 3H), 1.17 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 498 [M + H]⁺. 752

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.57-7.55 (m, 1H), 7.47-7.45 (m, 1H),4.88-4.75 (m, 3H), 4.56-4.50 (m, 1H), 4.14-4.10 (m, 1H), 3.79 (s, 3H),3.21-3.12 (m, 1H), 2.97-2.90 (m, 1H), 2.58-2.52 (m, 1H), 2.42-2.36 (m,2H), 2.28-2.20 (m, 3H), 2.06-2.03 (m, 2H), 1.80-1.61 (m, 11H), 1.14 (d,J = 6.8 Hz, 3H). LCMS (ES, m/z): 470 [M + H]⁺. 753

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.57-7.48 (m, 2H), 7.44-7.35 (m, 2H),6.24-6.22 (m, 1H), 5.03-4.98 (m, 1H), 4.88-4.86 (m, 1H), 4.74-4.68 (m,1H), 4.24-4.17 (m, 1H), 3.78 (s, 3H), 3.12-3.02 (m, 1H), 3.01-2.95 (m,1H), 2.91-2.75 (m, 1H), 2.65-2.12 (m, 5H), 1.95-1.55 (m, 5H), 1.41-1.30(m, 2H), 1.30-1.02 (m, 5H). LCMS (ES, m/z): 492 [M + H]⁺. 754

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.50 (d, J = 1.6 Hz, 1H), 7.38-7.36 (m,3H), 6.13-6.12 (m, 1H), 4.80-4.60 (m, 3H), 4.55-4.45 (m, 1H), 4.02-3.89(m, 1H), 3.79 (s, 3H), 3.56-3.38 (m, 2H), 3.28-2.99 (m, 3H), 2.95-2.81(m, 3H), 2.31-2.11 (m, 2H), 1.65-1.55 (m, 2H), 1.43 (d, J = 7.2 Hz, 3H),1.13 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 486 [M + H]⁺. 755

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.58-8.44 (m, 3H), 7.52 (d, J = 8.8 Hz,1H), 7.38 (d, J = 9.2 Hz, 1H), 4.82-4.75 (m, 3H), 3.78 (s, 3H),3.51-3.42 (m, 3H), 3.32-2.12 (m, 1H), 2.29-2.86 (m, 2H), 2.41-2.23 (m,5H), 1.89-1.65 (m, 5H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 478[M + H]⁺. 756

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.11 (s, 1H), 7.59-7.44 (m, 2H),7.27-7.15 (m, 4H), 4.86-4.70 (m, 1H), 4.52-4.37 (m, 1H), 4.31-4.20 (m,1H), 4.00-3.89 (m, 1H), 3.86 (s, 3H), 3.61-3.49 (m, 2H), 3.46-3.36 (m,1H), 3.22-3.07 (m, 1H), 3.05-2.80 (m, 3H), 2.55-2.35 (m, 1H), 2.32-2.18(m, 1H), 2.12-2.01 (m, 1H), 1.98-1.82 (m, 2H), 1.81-1.67 (m, 1H), 1.22(d, J = 6.9 Hz, 6H), 1.14 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 520 [M +H]⁺. 757

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48-7.41 (m, 2H), 7.32-7.25 (m, 5H),4.76-4.74 (m, 1H), 4.53-4.50 (m, 1H), 4.26-4.24 (m, 1H), 3.76-3.71 (m,4H), 3.69-3.65 (m, 1H), 3.42-3.31 (m, 4H), 3.14-3.11 (m, 1H), 2.90-2.86(m, 1H), 2.33-2.30 (m, 1H), 2.22-2.09 (m, 2H), 2.01-1.96 (m, 1H),1.78-1.74 (m, 1H), 1.64-1.50 (m, 3H), 1.31-1.28 (m, 1H), 1.14-1.12 (m,4H). LCMS (ES, m/z): 506 [M + H]+. 758

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.03 (d, J = 8.0 Hz, 1H), 7.56 (d, J =9.2 Hz, 1H), 7.51-7.43 (m, 2H), 7.38-7.36 (m, 1H), 7.27 (d, J = 6.8 Hz,1H), 5.54-5.49 (m, 1H), 4.87-4.84 (m, 1H), 4.82-4.74 (m, 2H), 3.79 (s,3H), 3.72-3.50 (m, 2H), 3.23-3.05 (m, 2H), 3.03-2.96 (m, 3H), 2.48-2.25(m, 5H), 1.80-1.59 (m, 5H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z):531 [M + H]⁺. 759

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.57 (d, J = 9.0 Hz, 1H), 7.47 (d, J =9.3 Hz, 1H), 4.97-4.92 (m, 2H), 4.81-4.78 (m, 1H), 4.61-4.56 (m, 1H),3.93-3.90 (m, 2H), 3.79 (s, 3H), 3.74-3.70 (m, 1H), 3.51-3.48 (m, 2H),3.22-3.17 (m, 1H), 2.99-2.94 (m, 1H), 2.64-2.50 (m, 1H), 2.41-2.35 (m,2H), 2.30-2.16 (m, 3H), 2.13-1.92 (m, 4H), 1.83-1.53 (m, 5H), 1.14 (d, J= 6.6 Hz, 3H). LCMS (ES, m/z): 486 [M + H]⁺. 760

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53 (d, J = 8.8 Hz, 1H), 7.37 (d, J =8.8 Hz, 1H), 4.83-4.73 (m, 2H), 3.78 (s, 3H), 3.21-3.15 (m, 1H),3.14-3.12 (m, 1H), 2.92-2.89 (m, 4H), 2.60-2.55 (m, 1H), 2.42-2.39 (m,2H), 2.32-2.22 (m, 3H), 2.12-2.05 (m, 2H), 2.02-1.96 (m, 2H), 1.90-1.84(m, 3H), 1.78-1.55 (m, 6H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):493 [M + H]⁺. 761

LCMS (ES, m/z): 507 [M + H]⁺ 762

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56 (d, J = 9.2 Hz, 1H), 7.44 (d, J =9.2 Hz, 1H), 3.31-5.26 (m, 1H), 4.78-4.76 (m, 2H), 3.79 (s, 3H),3.17-3.14 (m, 1H), 3.01-2.98 (m, 1H), 2.94-2.84 (m, 2H), 2.53-2.52 (m,1H), 2.37-2.25 (m, 4H), 2.23-2.08 (m, 1H), 1.77-1.56 (m, 10H), 1.36-1.25(m, 1H), 1.23-1.20 (m, 1H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):470 [M + H]⁺. 763

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.45 (d, J = 8.8 Hz, 1H), 7.32 (d, J =8.8 Hz, 1H), 7.25-7.05 (m, 5H), 4.95-4.90 (m, 1H), 4.80-4.65 (m, 1H),3.75 (s, 3H), 3.65-3.55 (m, 1H), 3.40-3.30 (m, 1H), 3.25-3.15 (m, 1H),3.05-2.80 (m, 3H), 2.41-2.22 (m, 4H), 2.00-1.90 (m, 1H), 1.89-1.60 (m,5H), 1.36 (d, J = 6.8 Hz, 3H), 1.13 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z):490 [M + H]⁺. 764

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.57-7.50 (m, 1H), 7.43-7.36 (m, 1H),4.79-4.70 (m, 2H), 4.46-4.36 (m, 1H), 3.78 (s, 3H), 3.70-3.60 (m, 1H),3.58-3.41 (m, 2H), 3.29-3.13 (m, 2H), 2.99-2.85 (m, 2H), 2.55-2.43 (m,1H), 2.41-2.19 (m, 4H), 2.02-1.80 (m, 6H), 1.80-1.58 (m, 6H), 1.14 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 497 [M + H]⁺. 765

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.16-8.06 (m, 1H), 7.74-7.64 (m, 1H),7.53 (d, J = 9.2 Hz, 1H), 7.41 (d, J = 9.2 Hz, 1H), 6.97 (t, J = 6.4 Hz,1H), 6.88 (d, J = 8.4 Hz, 1H), 6.67-6.53 (m, 1H), 4.82-4.63 (m, 2H),3.78 (s, 3H), 3.29-3.11 (m, 1H), 2.95-2.82 (m, 1H), 2.57-2.31 (m, 3H),2.30-2.12 (m, 3H), 2.09-1.98 (m, 1H), 1.94-1.81 (m, 4H), 1.77-1.59 (m,2H), 1.58-1.43 (m, 1H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 493[M + H]⁺. 766

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.30-7.21 (m, 2H), 4.77-4.65 (m, 1H),4.60-4.53 (m, 2H), 4.33-4.23 (m, 1H), 3.77 (s, 3H), 3.19-3.07 (m, 1H),2.84-2.72 (m, 1H), 2.48-2.37 (m, 1H), 2.33-2.12 (m, 5H), 2.10-2.00 (m,1H), 1.98-1.84 (m, 6H), 1.75-1.55 (m, 7H), 1.32-1.24 (m, 2H), 1.13 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 484 [M + H]⁺. 767

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53-7.25 (m, 6H), 7.24-7.18 (m, 1H),4.78-4.67 (m, 1H), 4.63-4.55 (m, 2H), 4.37-4.26 (m, 1H), 3.78 (s, 3H),3.19-3.04 (m, 2H), 2.92-2.80 (m, 2H), 2.52-2.41 (m, 1H), 2.31-2.18 (m,6H), 2.06-1.95 (m, 2H), 1.85-1.77 (m, 1H), 1.74-1.61 (m, 3H), 1.14 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 506 [M + H]⁺. 768

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.52-7.50 (m, 2H), 7.41-7.38 (m, 1H),7.33-7.29 (m, 3H), 4.80-4.50 (m, 2H), 4.25-3.89 (m, 7H), 3.75-3.55 (m,2H), 3.40-2.83 (m, 3H), 2.45-2.15 (m, 2H), 1.85-1.45 (m, 4H), 1.14 (d, J= 6.9 Hz, 3H). LCMS (ES, m/z): 512 [M + H]⁺. 769

LCMS (ES, m/z): 502 [M + H]⁺ 770

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55-7.50 (m, 1H), 7.43-7.41 (m, 1H),7.17-7.12 (m, 1H), 6.79-6.77 (m, 1H), 6.54 (s, 1H), 4.87-4.70 (m, 2H),3.83-3.50 (m, 9H), 3.33-3.16 (m, 1H), 2.93-2.82 (m, 2H), 2.51-2.46 (m,1H), 2.35-2.32 (m, 1H), 2.22-2.20 (m, 3H), 2.05-2.02 (m, 1H), 1.92-1.88(m, 1H), 1.70-1.68 (m, 3) 1.44 (d, J = 4.0 Hz, 3H). LCMS (ES, m/z): 556[M + H]⁺ 771

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53-7.40 (m, 4H), 6.18-6.12 (m, 1H),5.55-5.38 (m, 1H), 4.80-4.50 (m, 3H), 3.98-3.85 (m, 1H), 3.75 (s, 3H),3.54-3.15 (m, 5H), 2.98-2.75 (m, 2H), 2.62-2.48 (m, 1H), 2.29-2.15 (m,1H), 1.75-1.68 (m, 1H), 1.43 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.6 Hz,3H). LCMS (ES, m/z): 472 [M + H]⁺ 772

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.86 (s, 2H), 7.70 (s, 1H), 7.42 (s,1H), 6.33-6.28 (m, 1H), 5.80-5.55 (m, 1H), 4.92-4.65 (m, 2H), 4.32-4.15(m, 1H), 3.82-3.75 (m, 4H), 3.55-3.38 (m, 2H), 3.38-2.98 (m, 4H),2.88-2.65 (m, 1H), 2.35-2.15 (m, 2H), 1.98-1.78 (m, 1H), 1.61 (d, J =7.2 Hz, 3H), 1.22 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 472 [M + H]⁺. 773

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.50 (d, J = 8.8 Hz, 1H), 7.45-7.33 (m,3H), 7.10-6.98 (m, 2H), 4.80-4.67 (m, 1H), 4.54-4.39 (m, 1H), 4.30-4.17(m, 1H), 4.12-4.02 (m, 1H), 4.02-3.92 (m, 2H), 3.76 (s, 3H), 3.73-3.63(m, 1H), 3.61-3.50 (m, 1H), 3.30-3.24 (m, 1H), 3.22-3.09 (m, 1H),2.94-2.83 (m, 1H), 2.45-2.30 (m, 1H), 2.26-2.12 (m, 1H), 1.81-1.66 (m,3H), 1.46-1.41 (m, 1H), 1.10 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 496[M + H]⁺. 774

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56 (d, J = 9.2 Hz, 1H), 7.41 (d, J =9.2 Hz, 1H), 5.11-5.06 (m, 1H), 4.78-4.73 (m, 2H), 3.79 (s, 3H),3.21-3.17 (m, 1H), 3.01-2.99 (m, 1H), 2.95-2.90 (m, 1H), 2.70-2.68 (m,1H), 2.50-2.23 (m, 5H), 1.97-1.76 (m, 3H), 1.75-1.57 (m, 9H), 1.23-1.19(m, 1H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 470 [M + H]⁺. 775

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.15-8.04 (m, 2H), 7.54-7.50 (m, 1)7.49-7.45 (m, 1H), 7.31-7.30 (m, 1H), 4.78-4.71 (m, 2H), 4.69-4.60 (m,1H), 4.49-4.31 (m, 2H), 3.79 (s, 3H), 3.25-3.20 (m, 1H), 3.02-2.95 (m,2H), 2.41-2.12 (m, 5H), 1.82-1.69 (m, 3H), 1.40-1.31 (m, 8H), 1.16 (d, J= 6.4 Hz, 3H). LCMS (ES, m/z): 521 [M + H]⁺ 776

LCMS (ES, m/z): 493 [M + H]⁺ 777

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.25-8.15 (m, 2H), 7.98-7.88 (m, 2H),4.98-4.82 (m, 4H), 3.84 (s, 3H), 3.16-2.98 (m, 2H), 2.95 (s, 1H),2.49-2.34 (m, 2H), 2.32-2.14 (m, 3H), 2.09-2.03 (m, 1H), 2.00-1.86 (m,2H), 1.86-1.75 (m, 1H), 1.54-1.40 (m, 1H), 1.20 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 532 [M + H]⁺. 778

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.19 (d, J = 7.6 Hz, 1H), 7.83 (s, 2H),7.71-7.63 (m, 1H), 7.61-7.53 (m, 1H), 7.46 (d, J = 7.6 Hz, 1H), 5.01 (s,2H), 4.91-4.95 (m, 1H), 4.84-4.77 (m, 1H), 4.15-4.05 (m, 2H), 3.82 (s,3H), 3.55-3.44 (m, 2H), 3.12-2.99 (m, 1H), 2.98-2.87 (m, 1H), 2.69-2.50(m, 2H), 2.30-2.17 (m, 1H), 1.90-1.78 (m, 3H), 1.16 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 464 [M + H]⁺. 779

¹H-NMR (DMSO, 400 MHz) δ (ppm): 12.48-11.85 (br, 1H), 7.85-7.71 (m, 2H),7.64 (d, J = 6.0 Hz, 1H), 7.48-7.32 (m, 4H), 6.59-6.41 (m, 1H),4.72-4.65 (m, 1H), 4.60-4.41 (m, 1H), 3.79 (s, 3H), 3.25 (s, 3H),3.23-3.12 (m, 1H), 3.02-2.91 (m, 1H), 2.50-2.41 (m, 1H), 2.38-2.25 (m,1H), 2.25-2.12 (m, 1H), 2.09-1.91 (m, 3H), 1.84-1.79 (m, 1H), 1.79-1.61(m, 2H), 1.41-1.26 (m, 1H), 1.16 (d, J = 10.0 Hz, 3H). 1.01-0.95 (m,1H). LCMS (ES, m/z): 540 [M + H]⁺. 780

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.65-7.41 (m, 3H), 6.84-6.82 (m, 1H),6.61-6.59 (m, 1H), 5.22-5.12 (m, 1H), 4.85-4.79 (m, 1H), 4.49-4.39 (m,3H), 3.81 (s, 3H), 3.21-3.19 (m, 1H), 2.98-2.94 (m, 1H), 2.47-2.44 (m,1H), 2.35-2.17 (m, 3H), 2.17-2.08 (m, 2H), 1.17 (m, 1H), 1.62 (m, 2H),1.51-1.48 (m, 2H), 1.35-1.22 (m, 6H), 1.25-0.99 (m, 3H). LCMS (ES, m/z):521 [M + H]⁺ 781

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.45-8.43 (m, 1H), 8.15-7.90 (m, 2H),7.84 (s, 2H), 7.43-7.41 (m, 1H), 5.15-5.04 (m, 1H), 4.84-4.72 (m, 1H),3.83 (s, 3H), 3.24-3.20 (m, 1H), 3.17-3.05 (m, 1H), 2.95-2.92 (m, 1H),2.53-2.50 (m, 1H), 2.43-2.41 (m, 1H), 2.37-2.31 (m, 1H), 2.22 (s, 3H),2.13-1.99 (m, 2H), 1.88-1.82 (m, 1H), 1.75-1.50 (m, 2H), 1.23-1.10 (m,4H), 0.99-0.71 (m, 1H). LCMS (ES, m/z): 493 [M + H]⁺. 782

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.92-7.76 (m, 2H), 7.67-7.56 (m, 1H),6.05 (s, 1H), 5.12-5.07 (m, 1H), 4.72-4.56 (m, 2H), 4.24-4.05 (m, 1H),3.81 (s, 3H), 3.21-2.86 (m, 3H), 2.51-2.31 (m, 2H), 2.31-2.09 (m, 3H),2.09-1.76 (m, 7H), 1.73-1.48 (m, 5H), 1.18 (d, J = 6.9 Hz, 3H). LCMS(ES, m/z): 494 [M + H]⁺ 783

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.57-7.54 (m, 1H), 7.46-7.43 (m, 1H),7.24-7.06 (m, 3H), 4.85-4.75 (m, 1H), 4.62-4.45 (m, 1H), 4.35-4.25 (m,1H), 4.15-3.95 (m, 3H), 3.80-3.55 (m, 5H), 3.40-3.10 (m, 2H), 2.98-2.85(m, 1H), 2.45-2.15 (m, 5H), 1.85-1.65 (m, 3H), 1.50-1.40 (m, 1H), 1.15(d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 510 [M + H]⁺. 784

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.54 (d, J = 9.2 Hz, 1H), 7.41 (d, J =8.8 Hz, 1H), 4.79-4.75 (m, 1H), 4.38-4.32 (m, 1H), 3.99-3.96 (m, 2H),3.79 (s, 3H), 3.48-3.42 (m, 2H), 3.20-3.12 (m, 1H), 3.07-3.03 (m, 2H),2.95-2.88 (m, 1H), 2.62-2.51 (m, 1H), 2.50-2.35 (m, 2H), 2.28-2.24 (m,3H), 2.01-1.98 (m, 2H), 1.80-1.69 (m, 8H), 1.42-1.33 (m, 2H), 1.14 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 484 [M + H]⁺. 785

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.59-7.47 (m, 5H), 7.41 (d, J = 8.8 Hz,1H), 6.91-6.56 (m, 1H), 4.86-4.67 (m, 2H), 4.42-4.32 (m, 1H), 4.16-4.04(m, 1H), 4.03-3.93 (m, 1H), 3.92-3.81 (m, 1H), 3.78 (s, 3H), 3.76-3.66(m, 1H), 3.32-3.26 (m, 2H), 3.23-3.11 (m, 1H), 2.98-2.78 (m, 2H),2.75-2.63 (m, 1H), 2.31-2.18 (m, 1H), 1.79-1.66 (m, 1H), 1.13 (d, J =6.8 Hz, 3H). LCMS (ES, m/z): 564 [M + H]⁺. 786

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49 (t, J = 8.0 Hz, 1H), 7.36 (d, J =8.8 Hz, 1H), 7.28-7.18 (m, 3H), 7.18-7.07 (m, 3H), 6.92-6.69 (m, 3H),4.81-4.68 (m, 1H), 4.33-4.23 (m, 1H), 3.84 (s, 3H), 3.75 (s, 3H),3.59-3.47 (m, 1H), 3.31-3.16 (m, 2H), 3.00-2.88 (m, 1H), 2.33-2.18 (m,1H), 1.81-1.67 (m, 1H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 500[M + H]⁺. 787

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.44-7.35 (m, 3H), 7.34-7.28 (m, 3H),7.04-6.94 (m, 1H), 4.79-4.68 (m, 1H), 4.64-4.58 (m, 1H), 3.78 (s, 3H),3.68 (s, 3H), 3.18-3.05 (m, 1H), 3.03-2.98 (m, 1H), 2.86-2.78 (m, 1H),2.48-2.31 (m, 2H), 2.28-2.17 (m, 3H), 2.05-1.92 (m, 1H), 1.95-1.87 (m,1H), 1.80-1.54 (m, 3H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 477[M + H]⁺. 788

LCMS (ES, m/z): 497 [M + H]⁺ 789

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53 (d, J = 9.2 Hz, 1H), 7.39 (d, J =8.4 Hz, 1H), 7.25-7.00 (m, 4H), 5.62-5.42 (m, 2H), 4.91-4.68 (m, 2H),3.77 (s, 3H), 3.33-2.79 (m, 7H), 2.46-2.19 (m, 5H), 1.91-1.63 (m, 5H),1.12 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 531 [M + H]⁺. 790

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53-7.19 (m, 3H), 6.06 (s, 1H),4.78-4.63 (m, 1H), 4.63-4.51 (m, 1H), 4.51-4.40 (m, 1H), 4.40-4.22 (m,1H), 4.05-3.91 (m, 1H), 3.76 (s, 3H), 3.27-3.11 (m, 1H), 3.01-2.78 (m,1H), 2.54-2.02 (m, 6H), 1.96-1.62 (m, 4H), 1.62-1.47 (m, 1H), 1.42-1.40(d, J = 6.9 Hz, 3H), 1.14-1.12 (d, J = 6.6 Hz, 3H). LCMS: (ES, m/z): 514[M + H]⁺. 791

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.30-7.19 (m, 7H), 4.29-4.23 (m, 1H),4.04-4.00 (m, 1H), 3.78 (s, 3H), 3.65-3.60 (m, 1H), 3.42-3.37 (m, 1H),3.35 (s, 3H), 3.18-3.14 (m, 2H), 2.91-2.88 (m, 1H), 2.13-2.11 (m, 1H),2.07-2.05 (m, 4H), 1.95-1.89 (m, 2H), 1.86-1.82 (m, 1H), 1.57-1.54 (m,1H), 1.33-1.30 (m, 1H), 1.21-1.15 (m, 1H), 1.16 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 506 [M + H]⁺. 792

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55-7.47 (m, 2H), 7.47-7.32 (m, 3H),7.29-7.19 (m, 2H), 5.56 (s, 2H), 4.75-4.65 (m, 1H), 4.33-4.22 (m, 1H),3.75 (s, 3H), 3.20-3.06 (m, 1H), 2.83-2.73 (m, 1H), 2.37-2.04 (m, 6H),1.92-1.80 (m, 2H), 1.71-1.52 (m, 3H), 1.12 (d, J = 6.8 Hz, 3H). LCMS(ES, m/z): 478 [M + H]⁺. 793

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.18-8.06 (m, 1H), 7.77-7.63 (t, J =7.2 Hz, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.41 (d, J = 9.2 Hz, 1H), 6.96(t, J = 6.0 Hz, 1H), 6.87 (d, J = 8.4 Hz, 1H), 6.68-6.54 (m, 1H),4.80-4.64 (m, 2H), 3.78 (s, 3H), 3.26-3.11 (m, 1H), 2.99-2.85 (m, 1H),2.56-2.44 (m, 1H), 2.43-2.30 (m, 2H), 2.28-2.11 (m, 3H), 2.08-1.96 (m,1H), 1.90-1.76 (m, 4H), 1.75-1.57 (m, 2H), 1.56-1.39 (m, 1H), 1.12 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 493 [M + H]⁺. 794

¹H NMR (400 MHz, CD₃OD) δ (ppm): 7.80 (d, J = 9.2 Hz, 1H), 7.74 (d, J =9.2 Hz, 1H), 5.39-5.37 (m, 1H), 4.95-4.92 (m, 1H), 4.83-4.81 (m, 1H),3.98-3.88 (m, 2H), 3.82 (s, 3H), 3.73-3.70 (m, 1H), 3.50-3.41 (m, 2H),3.15-3.11 (m, 1H), 3.00-2.95 (m, 1H), 2.64-2.51 (m, 1H), 2.48-2.45 (m,2H), 2.31-2.24 (m, 3H), 2.13-2.06 (m, 3H), 1.86-1.83 (m, 2H), 1.76-1.58(m, 7H), 1.16 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 500 [M + H]⁺ 795

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.43 (s, 1H), 7.71 (d, J = 3.6 Hz, 1H),7.53 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 6.61 (d, J = 3.6 Hz,1H), 4.89-4.87 (m, 1H), 4.80-4.69 (m, 3H), 3.79 (s, 3H), 3.24-3.17 (m,1H), 2.98-2.92 (m, 2H), 2.43-2.17 (m, 5H), 1.79-1.60 (m, 4H), 1.43-1.31(m, 1H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 503 [M + H]⁺. 796

LCMS (ES, m/z): 510 [M + H]⁺ 797

¹H-NMR (DMSO, 400 MHz) δ (ppm): 7.67-7.25 (m, 7H), 6.12-5.79 (m, 1H),4.75-4.58 (m, 1H), 4.47-4.28 (m, 1H), 3.67 (s, 3H), 3.20-3.04 (m, 1H),2.98-2.78 (m, 1H), 2.62 (s, 1H), 2.45 (s, 2H), 2.41-2.22 (m, 2H),2.20-2.08 (m, 1H), 2.08-1.86 (m, 3H), 1.85-1.74 (m, 1H), 1.74-1.54 (m,2H), 1.29-1.14 (m, 1H), 1.09 (d, J = 6.8 Hz, 3H), 1.02-0.79 (m, 1H).LCMS (ES, m/z): 524 [M + H]⁺. 798

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53 (d, J = 6.8 Hz, 1H), 7.43-7.40 (d,J = 6.8 Hz, 1H), 4.91-4.89 (m, 2H), 4.85-4.76 (m, 1H), 4.72-4.54 (m,1H), 3.79-3.69 (m, 5H), 3.51-3.45 (m, 2H), 3.17-3.14 (m, 1H), 2.97-2.90(m, 2H), 2.35-2.21 (m, 5H), 2.11-1.95 (m, 6H), 1.78-1.72 (m, 2H),1.64-1.48 (m, 1H).1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 483 [M + H]+799

LCMS (ES, m/z): 511 [M + H]⁺ 800

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52-7.45 (m, 1H), 7.45-7.31 (m, 5H),7.31-7.23 (m, 1H), 5.17-5.07 (m, 1H), 4.83-4.71 (m, 1H), 4.40-4.28 (m,1H), 3.79 (s, 3H), 3.51-3.40 (m, 1H), 3.40-3.35 (m, 1H), 3.24-3.11 (m,1H), 3.00-2.86 (m, 1H), 2.52-2.45 (m, 1H), 2.42-2.13 (m, 4H), 2.13-2.03(m, 1H), 1.96-1.86 (m, 1H), 1.82-1.71 (m, 1H), 1.72-1.64 (m, 1H),1.58-1.51 (m, 2H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 492 [M +H]⁺. 801

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.54 (s, 1H), 8.45 (s, 1H), 8.38 (d, J= 2.8 Hz, 1H), 7.45 (d, J = 9.2 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H),4.84-4.74 (m, 1H), 4.50-4.35 (m, 1H), 4.01-3.85 (m, 1H), 3.79 (s, 3H),3.60-3.45 (m, 1H), 3.25-3.11 (m, 2H), 2.96-2.81 (m, 1H), 2.60-2.49 (m,1H), 2.46-2.11 (m, 5H), 2.01-1.85 (m, 1H), 1.79-1.61 (m, 3H), 1.61-1.51(m, 1H), 1.50 (d, J = 6.8 Hz, 3H), 1.13 (d, J = 6.8 Hz, 3H). LCMS (ES,m/z): 492 [M + H]⁺. 802

LCMS (ES, m/z): 481 [M + H]⁺ 803

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.45 (d, J = 8.8 Hz, 1H), 7.30 (d, J =9.2 4.80-4.71 (m, 1H), 4.27-4.13 (m, 1H), 3.79 (s, 3H), 3.68-3.55 (m,1H), 3.33-3.22 (m, 1H), 3.25-3.06 (m, 3H), 3.05-2.90 (m, 2H), 2.81-2.68(m, 1H), 2.55-2.44 (m, 1H), 2.39-2.22 (m, 2H), 2.20-2.02 (m, 1H),1.78-1.66 (m, 2H), 1.56 (d, J = 6.8 Hz, 3H), 1.15 (d, J = 6.8 Hz, 3H),0.56-0.43 (m, 1H). LCMS (ES, m/z): 447 [M + H]⁺. 804

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52 (d, J = 9.2 Hz, 1H), 7.39 (d, J =9.2 Hz, 1H), 4.83-4.69 (m, 2H), 4.02-3.83 (m, 2H), 3.82-3.69 (m, 4H),3.52-3.39 (m, 1H), 3.25-3.10 (m, 1H), 3.09-2.85 (m, 4H), 2.50-2.10 (m,7H), 2.03-1.80 (m, 4H), 1.80-1 55 (m, 4H), 1.14 (d, J = 6.8 Hz, 3H) LCMS(ES, m/z): 470 [M + H]⁺. 805

LCMS (ES, m/z): 495 [M + H]⁺ 806

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.61-7.48 (m, 1H), 7.43-7.24 (m, 1H),4.83-4.64 (m, 2H), 3.97-3.82 (m, 2H), 3.78 (s, 3H), 3.55-3.43 (m, 1H),3.38-3.35 (m, 1H), 3.24-3.11 (m, 1H), 3.10-2.74 (m, 4H), 2.56-2.33 (m,2H), 2.33-2.07 (m, 4H), 2.01-1.82 (m, 3H), 1.82-1.57 (m, 5H), 1.47-1.36(m, 1H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 470 [M + H]⁺. 807

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.40-7.30 (m, 4H), 7.29-7.22 (m, 2H),7.21-7.19 (m, 1H), 4.82-4.78 (m, 2H), 4.70-4.59 (m, 1H), 4.21-4.09 (m,1H), 3.76 (s, 3H), 3.20-3.15 (m, 2H), 3.12-3.05 (m, 1H), 2.81-2.78 (m,1H), 2.42-2.19 (m, 2H), 2.13-2.04 (m, 4H), 1.81-1.72 (m, 2H), 1.75-1.45(m, 3H), 1.13 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 492 [M + H]⁺. 808

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.54-7.51 (m, 1H), 7.42-7.39 (m, 1H),4.78-4.73 (m, 1H), 4.62 (m, 1H), 3.87-3.85 (m, 1H), 3.78-3.61 (m, 4H),3.28-2.84 (m, 2H), 2.72-2.66 (m, 1H), 2.50-2.18 (m, 5H), 2.15-2.05 (m,3H), 1.895 (m, 1H), 1.76-1.54 (m, 7H), 1.46 (d, J = 6.4 Hz, 3H),1.35-1.29 (m, 3H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 511 [M +H]⁺. 809

LCMS (ES, m/z): 477 [M + H]⁺ 810

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.93 (s, 1H), 7.51 (s, 1H), 7.38-7.22(m, 1H), 7.22-7.06 (m, 1H), 4.94-4.89 (m, 1H), 4.88-4.81 (m, 1H),4.81-4.65 (m, 1H), 4.65-4.44 (m, 3H), 3.76 (s, 3H), 3.18-3.01 (m, 1H),2.98-2.83 (m, 1H), 2.83-2.63 (m, 1H), 2.38-2.12 (m, 3H), 2.12-1.93 (m,2H), 1.87-1.71 (m, 2H), 1.71-1.51 (m, 3H), 1.13 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 516 [M + H]⁺. 811

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.94 (s, 1H), 7.59-7.54 (m, 2H), 7.28(d, J = 8.7 Hz, 1H), 5.15-4.98 (m, 1H), 4.70-4.40 (m, 3H), 3.98-3.81 (m,1H), 3.67 (s, 3H), 3.31-2.76 (m, 6H), 2.28-1.95 (m, 3H), 1.68-1.55 (m,1H), 1.23 (d, J = 6.9 Hz, 3H), 1.06 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z):457 [M + H]⁺. 812

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.45-7.42 (m, 1H), 7.41-7.34 (m, 3H),7.32-7.24 (m, 3H), 4.81-4.73 (m, 1H), 4.60-4.57 (m, 1H), 4.47-4.44 (m,1H), 4.43-4.17 (m, 2H), 3.76 (s, 3H), 3.30-3.27 (m, 1H), 2.98-2.93 (m,1H), 2.40-2.28 (m, 3H), 2.27-2.13 (m, 1H), 2.00-1.96 (m, 2H), 1.94-1.83(m, 1H), 1.80-1.73 (m, 1H), 1.71-1.57 (m, 1H), 1.17-1.13 (m, 4H),0.98-0.90 (m, 1H). LCMS (ES, m/z): 492 [M + H]⁺. 813

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.18 (d, J = 8.0 Hz, 2H), 7.78-7.75 (m,1H), 7.69-7.64 (m, 4H), 5.49-5.48 (m, 1H), 4.80-4.76 (m, 1H), 3.79 (s,3H), 3.23-3.16 (m, 1H), 3.06-2.99 (m, 2H), 2.52-2.48 (m, 1H), 2.25-2.17(m, 4H), 1.81-1.62 (m, 4H), 1.48-1.45 (m, 1H), 1.13 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 512 [M + H]⁺. 814

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.67 (s, 2H), 7.42-7.33 (m, 5H),5.54-5.51 (m, 1H), 5.04-5.01 (m, 1H), 4.84-4.78 (m, 1H), 3.81 (s, 3H),3.19-3.5 (m, 1H), 3.07-3.02 (m, 2H), 2.57-2.50 (m, 1H), 2.36-2.33 (m,1H), 2.26-2.23 (m, 3H), 1.86-1.67 (m, 4H), 1.63-1.55 (m, 1H), 1.38-1.34(m, 1H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 526 [M + H]⁺. 815

LCMS (ES, m/z): 497 [M + H]⁺ 816

LCMS (ES, m/z): 500 [M + H]⁺ 817

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.48 (d, J = 9.2 Hz, 1H), 7.39 (d, J =8.8 Hz, 1H), 7.27-7.23 (m, 2H), 7.20-7.17 (m, 3H), 5.29 (t, J = 7.2 Hz,1H), 4.78-4.75 (m, 1H), 4.68-4.62 (m, 1H), 3.78 (s, 3H), 3.33-3.32 (m,2H), 3.23-3.21 (m, 1H), 2.93-2.89 (m, 1H), 2.50-2.48 (m, 1H), 2.40-2.30(m, 1H), 2.27-2.20 (m, 3H), 2.16-2.09 (m, 1H), 1.97-1.92 (m, 1H),1.75-1.70 (m, 1H), 1.65-1.61 (m, 1H), 1.56-1.51 (m, 2H), 1.15 (d, J =6.8 Hz, 3H). LCMS (ES, m/z): 492 [M + H]⁺ 818

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51 (d, J = 8.8 Hz, 1H), 7.40 (d, J =8.4 Hz, 1H), 4.79-4.71 (m, 1H), 4.46-4.35 (m, 1H), 3.78 (s, 3H),3.22-3.15 (m, 1H), 2.95-2.87 (m, 3H), 2.62-2.58 (m, 1H), 2.50-2.35 (m,3H), 2.35-2.22 (m, 1H), 2.20-2.03 (m, 5H), 2.01-1.88 (m, 5H), 1.80-1.52(m, 5H), 1.14 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 454 [M + H]⁺. 819

LCMS (ES, m/z): 488 [M + H]⁺ 820

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.52 (d, J = 4.2 Hz, 1H), 7.58 (d, J =9.0 Hz, 1H), 7.43 (d, J = 9.0 Hz, 1H), 7.23 (d, J = 5.1 Hz, 1H),4.88-4.49 (m, 4H), 3.79 (s, 3H), 3.28-3.09 (m, 1H), 2.99-2.81 (m, 2H),2.48 (s, 3H), 2.43-2.12 (m, 5H), 1.93-1.53 (m, 4H), 1.53-1.41 (m, 1H),1.16-1.14 (d, J = 6.9 Hz, 3H). LCMS (ES, m/z): 478 [M + H]⁺ 821

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48 (d, J = 8.8 Hz, 1H), 7.41 (d, J =8.8 Hz, 1H), 7.27-7.14 (m, 4H), 6.92-6.90 (m, 1H), 5.15-5.04 (m, 1H),4.73-4.50 (m, 1H), 3.77 (s, 3H), 3.23-3.15 (m, 1H), 2.94-2.85 (m, 1H),2.60-2.49 (m, 1H), 2.41-2.18 (m, 5H), 1.89-1.70 (m, 2H), 1.86-1.65 (m,5H), 1.54-1.46 (m, 2H), 1.13 (d, J = 6.8 Hz, 3H) LCMS (ES, m/z): 504[M + H]⁺. 822

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53 (d, J = 9.2 Hz, 1H), 7.40 (d, J =8.4 Hz, 1H), 7.36-7.14 (m, 5H), 5.32-5.27 (m, 1H), 5.08-4.98 (m, 1H),4.82-4.68 (m, 1H), 3.79 (s, 3H), 3.45-3.41 (m, 1H), 3.25-3.21 (m, 2H),3.01-2.95 (m, 2H), 2.41-2.18 (m, 4H), 2.16-2.02 (m, 1H), 1.98-1.82 (m,2H), 1.78-1.59 (m, 3H), 1.15 (d, J = 6.4, 3H). LCMS (ES, m/z): 492 [M +H]⁺ 823

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.51 (s, 1H), 8.18-8.10 (m, 2H),7.47-7.35 (m, 2H), 5.12-5.07 (m, 1H), 4.82-4.74 (m, 1H), 3.77 (s, 3H),3.23-3.15 (m, 1H), 3.00-2.89 (m, 1H), 2.53-2.42 (m, 1H), 2.39-2.30 (m,2H), 2.32-2.15 (m, 3H), 2.02-1.71 (m, 7H), 1.69-1.57 (m, 2H), 1.13 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 506 [M + H]⁺. 824

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): ) 7.47-7.29 (m, 2H), 7.22 (d, J = 2.1Hz, 1H), 5.90 (s, 1H), 4.79-4.65 (m, 1H), 4.59-4.47 (m, 1H), 4.46-4.34(m, 1H), 4.34-4.18 (m, 1H), 4.00-3.82 (m, 1H), 3.76 (s, 3H), 3.26-3.16(m, 1H), 2.98-2.83 (m, 1H), 2.58-2.38 (m, 1H), 2.38-2.03 (m, 8H),1.93-1.80 (m, 1H), 1.80-1.56 (m, 3H), 1.49-1.35 (m, 4H), 1.14 (d, J =6.6 Hz, 3H). LCMS (ES, m/z): 494 [M + H]⁺ 825

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.90 (s, 1H), 7.87-7.75 (m, 2H), 7.31(s, 1H), 5.12-5.02 (m, 1H), 4.87-4.72 (m, 1H), 4.71 (d, J = 6.8 Hz, 2H),4.30-4.15 (m, 1H), 3.79 (s, 3H), 3.18-2.96 (m, 3H), 2.45-2.30 (m, 2H),2.29-2.18 (m, 2H), 2.14-1.99 (m, 2H), 1.95-1.70 (m, 3H), 1.65-1.60 (m,1H), 1.57 (d, J = 6.8 Hz, 3H), 1.16 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):514 [M + H]⁺. 826

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.64-7.52 (m, 1H), 7.52-7.41 (m, 1H),7.41-7.31 (m, 1H), 7.31-7.19 (m, 1H), 7.07-6.91 (m, 1H), 6.60 (s, 1H),5.63-5.42 (m, 1H), 5.42-5.26 (m, 1H), 4.86-4.58 (m, 4H), 3.79 (s, 3H),3.32-3.18 (m, 1H), 3.04-2.92 (m, 1H), 2.84-2.61 (m, 1H), 2.44-2.21 (m,3H), 2.13-1.93 (m, 2H), 1.91-1.72 (m, 3H), 1.72-1.43 (m, 2H), 1.18 (d, J= 6.4 Hz, 3H). LCMS (ES, m/z): 520 [M + H]⁺ 827

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.11-7.46 (m, 3H), 6.20 (s, 1H),5.28-5.01 (m, 1H), 4.79-4.48 (m, 2H), 4.30-4.01 (m, 1H), 3.80 (s, 3H),3.22-2.87 (m, 3H), 2.64-2.31 (m, 2H), 2.31-2.11 (m, 3H), 2.11-1.79 (m,4H), 1.73-1.48 (m, 4H), 1.32-1.23 (m, 1H), 1.16 (d, J = 6.6 Hz, 3H).LCMS (ES, m/z): 514 [M + H]⁺. 828

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.74 (s, 2H), 7.56 (d, J = 9.2 Hz, 1H),7.42 (d, J = 8.8 Hz, 1H), 4.82-4.65 (m, 2H), 3.79 (s, 3H), 3.17 (m, 1H),2.97-2.87 (m, 2H), 2.45-2.16 (m, 6H), 1.92-1.54 (m, 6H), 1.15 (d, J =6.4 Hz, 3H). LCMS (ES, m/z): 498 [M + H]⁺. 829

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.55 (d, J = 9.0 Hz, 1H), 7.44 (d, J =9.3 Hz, 1H), 7.25 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.1 Hz, 2H),4.86-4.80 (m, 1H), 4.78-4.54 (m, 1H), 4.29-4.24 (m, 1H), 3.99-3.92 (m,2H), 3.78-3.54 (m, 5H), 3.38-3.11 (m, 3H), 2.95-2.90 (m, 1H), 2.53-2.34(m, 1H), 2.33-1.69 (m, 8H), 1.14 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z):492 [M + H]⁺. 830

LCMS (ES, m/z): 503 [M + H]⁺ 831

LCMS (ES, m/z): 497 [M + H]⁺ 832

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53 (d, J = 9.0 Hz, 1H), 7.39 (d, J =9.0 Hz, 1H), 4.83-4.66 (m, 1H), 4.47-4.26 (m, 1H), 3.78 (s, 3H),3.33-3.32 (m, 3H), 3.28-3.06 (m, 2H), 3.01-2.82 (m, 3H), 2.58-2.35 (m,3H), 2.34-2.17 (m, 3H), 2.16-2.03 (m, 2H), 2.02-1.86 (m, 2H), 1.85-1.55(m, 6H), 1.31-1.07 (m, 7H). LCMS (ES, m/z): 498 [M + H]⁺. 833

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.34 (s, 1H), 8.15-8.10 (m, 2H),7.61-7.40 (m, 2H), 6.59 (t, J = 6.4 Hz, 1H), 4.79-4.62 (m, 2H), 3.77 (s,3H), 3.23-3.11 (m, 1H), 2.95-2.83 (m, 1H), 2.62-2.31 (m, 3H), 2.30-2.12(m, 4H), 1.98-1.90 (m, 1H), 1.88 (d, J = 6.8 Hz, 3H), 1.78-1.51 (m, 3H),1.13 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 494 [M + H]+. 834

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53-7.49 (m, 2H), 7.31 (s, 1H), 7.20(s, 1H), 5.55-5.35 (m, 1H), 4.97 (s, 1H), 4.78-4.32 (m, 2H), 3.95-3.85(m, 1H), 3.75-3.58 (m, 3H), 3.52-3.15 (m, 5H), 2.98-2.65 (m, 2H),2.32-2.12 (m, 2H), 1.95 (s, 3H), 1.76-1.66 (m, 1H), 1.41 (d, J = 6.9 Hz,3H), 1.12 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 486 [M + H]⁺. 835

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.54-7.29 (m, 7H), 6.57 (s, 1H),4.82-4.69 (m, 1H), 4.35-4.18 (m, 1H), 3.79 (s, 3H), 3.30-3.19 (m, 1H),3.04-2.90 (m, 1H), 2.52-1.85 (m, 10H), 1.85-1.54 (m, 2H), 1.40-1.25 (m,1H), 1.18 (d, J = 6.6 Hz, 3H), 1.13-1.01 (m, 1H). LCMS (ES, m/z): 519[M + H]⁺ 836

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.82-7.59 (m, 3H), 7.37 (s, 1H),5.22-5.02 (m, 1H), 4.83-4.78 (m, 1H), 4.61 (d, J = 7.2 Hz, 2H),4.24-3.97 (m, 1H), 3.80 (s, 3H), 3.57-3.44 (m, 2H), 3.42-3.32 (m, 2H),3.21-2.89 (m, 4H), 2.89-2.70 (m, 1H), 2.70-2.49 (m, 1H), 2.33-2.12 (m,3H), 1.93-1.76 (m, 1H), 1.55 (d, J = 6.9 Hz, 3H), 1.15 (d, J = 6.6 Hz,3H). LCMS (ES, m/z): 497 [M + H]⁺. 837

LCMS (ES, m/z): 494 [M + H]⁺ 838

LCMS (ES, m/z): 478 [M + H]⁺ 839

LCMS (ES, m/z): 497 [M + H]⁺ 840

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51-7.38 (m, 2H), 7.34-7.26 (m, 2H),7.23-7.19 (m, 3H), 4.81-4.63 (m, 2H), 4.62-4.38 (m, 2H), 3.77 (s, 3H),3.74 (s, 3H), 3.25-3.13 (m, 1H), 3.02-3.86 (m, 2H), 2.55-2.03 (m, 5H),1.79-1.53 (m, 3H), 1.30-1.15 (m, 2H), 1.13 (d, J = 6.8, 3H). LCMS (ES,m/z): 476 [M + H]⁺. 841

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.63-7.46 (m, 1H), 7.46-7.28 (m, 1H),4.86-4.68 (m, 2H), 3.92-3.76 (m, 5H), 3.58-3.39 (m, 1H), 3.31-3.11 (m,2H), 3.09-2.89 (m, 4H), 2.53-2.35 (m, 2H), 2.35-2.12 (m, 4H), 2.01-1.85(m, 3H), 1.84-1.54 (m, 5H), 1.51-1.37 (m, 1H), 1.15 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 470 [M + H]⁺. 842

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55 (s, 1H), 7.52-7.33 (m, 3H),4.82-4.72 (m, 1H), 4.71-4.57 (m, 2H), 4.56-4.44 (m, 1H), 4.04-3.89 (m,1H), 3.79 (s, 3H), 3.47-3.34 (m, 3H), 3.28-3.14 (m, 2H), 3.07-2.89 (m,1H), 2.74-2.60 (m, 1H), 2.59-2.40 (m, 1H), 2.35-2.21 (m, 1H), 2.17-1.85(m, 3H), 1.84-1.62 (m, 2H), 1.46 (d, J = 7.2 Hz, 3H), 1.15 (d, J = 6.8Hz, 3H). LCMS (ES, m/z): 485 [M + H]⁺. 843

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.43-7.37 (m, 3H), 7.32-7.26 (m, 3H),6.99 (t, J = 7.6 Hz, 1H), 4.73-4.69 (m, 1H), 4.42-4.40 (m, 1H), 3.76 (s,3H), 3.09-3.03 (m, 1H), 2.82-2.76 (m, 1H), 2.52-2.36 (m, 3H), 2.35-2.17(m, 3H), 2.01-1.99 (m, 2H), 1.70-1.62 (m, 3H), 1.12 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 463 M + H]⁺. 844

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53-7.40 (m, 2H), 7.31 (s, 1H), 7.17(s, 1H), 5.49-5.38 (m, 1H), 4.89-4.38 (m, 3H), 3.98-3.85 (m, 1H), 3.78(s, 3H), 3.50-3.15 (m, 3H), 2.98-2.20 (m, 4H), 2.60-2.15 (m, 2H), 1.96(s, 3H), 1.78-1.65 (m, 1H), 1.42 (d, J = 6.9 Hz, 3) 1.12 (d, J = 6.6 Hz,3H). LCMS (ES, m/z): 486 [M + H]⁺. 845

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.61 (d, J = 9.0 Hz, 1H), 7.49 (d, J =9.0 Hz, 1H), 7.24-7.11 (m, 1H), 7.07-7.04 (m, 2H), 4.81-4.57 (m, 2H),4.32-4.28 (m, 1H), 4.07-3.96 (m, 2H), 3.79 (s, 3H), 3.77-3.72 (m, 1H),3.58-3.45 (m, 1H), 3.42-3.33 (m, 2H), 3.14-3.09 (m, 1H), 2.96-2.92 (m,1H), 2.35-2.30 (m, 1H), 2.26-2.25 (m, 4H), 2.18-2.09 (m, 1H), 1.83-1.74(m, 2H), 1.44-1.43 (m, 1H), 1.14 (d, J = 6.9 Hz, 3H). LCMS (ES, m/z):510 [M + H]⁺. 846

LCMS (ES, m/z): 511 [M + H]⁺ 847

LCMS (ES, m/z): 477 [M + H]⁺ 848

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.51-8.35 (m, 3H), 7.48 (d, J = 9.2 Hz,1H), 7.35 (d, J = 8.8 Hz, 1H), 4.87-4.71 (m, 2H), 3.95-3.93 (m, 1H),3.78 (s, 3H), 3.68-3.63 (m, 1H), 3.34-3.18 (m, 2H), 2.97-2.88 (m, 2H),2.41-2.08 (m, 5H), 1.92-1.66 (m, 5H), 1.47 (d, J = 6.8 Hz, 3H), 1.13 (d,J = 6.8 Hz, 3H). LCMS (ES, m/z): 492 [M + H]⁺. 849

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.32 (d, J = 9.0 Hz, 1H), 7.23-7.08 (m,9H), 6.79 (d, J = 8.7 Hz, 1H), 4.85-4.70 (m, 1H), 4.45-4.25 (m, 1H),3.89 (s, 3H), 3.75 (s, 3H), 3.55-3.42 (m, 1H), 3.32-2.85 (m, 3H),2.32-2.21 (m, 1H), 1.75-1.58 (m, 1H), 1.14 (d, J = 6.9 Hz, 3H). LCMS(ES, m/z): 500 [M + H]⁺. 850

LCMS (ES, m/z): 494 [M + H]⁺ 851

LCMS (ES, m/z): 511 [M + H]⁺ 852

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.29-8.20 (m, 1H), 7.90-7.70 (m, 2H),7.55-7.30 (m, 6H), 5.05-5.01 (m, 1H), 4.82-4.71 (m, 1H), 4.2-3.7 (m,8H), 3.59-3.51 (m, 1H), 3.48-3.33 (m, 1H), 3.33-3.12 (m, 1H), 2.96-2.89(m, 1H), 2.35-2.18 (m, 1H), 2.18-1.93 (m, 1H), 1.78-1.72 (m, 1H),1.51-1.42 (m, 1H), 1.18-1.11 (m, 4H), 0.65 (m, 1H). LCMS (ES, m/z): 528[M + H]⁺ 853

LCMS (ES, m/z): 503 [M + H]⁺ 854

LCMS (ES, m/z): 493 [M + H]⁺ 855

¹H NMR (CD₃OD, 400 MHz) δ (ppm): 7.83-7.74 (m, 2H), 7.29-7.27 (m, 3H),7.18-7.17 (m, 2H), 5.67-5.63 (m, 1H), 4.86-4.84 (m, 1H), 4.50-4.42 (m,1H), 3.81 (s, 3H), 3.64-3.60 (m, 1H), 3.28-3.27 (m, 1H), 3.18-3.16 (m,1H), 3.01-2.95 (m, 1H), 2.53-2.49 (m, 1H), 2.32-2.25 (m, 4H), 2.04-1.88(m, 6H), 1.70-1.68 (m, 1H), 1.52-1.40 (m, 1H), 1.21 (d, J = 6.4 Hz, 3H),0.50-0.48 (m, 1H). LCMS (ES, m/z): 533 [M + H]⁺. 856

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.54 (s, 1H), 8.38 (s, 1H), 8.00 (s,1H), 7.59 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 4.84-4.74 (m,2H), 3.79 (s, 3H), 3.33-3.15 (m, 1H), 3.03-2.96 (m, 1H), 2.86-2.82 (m,1H), 2.52-2.05 (m, 6H), 1.89-1.55 (m, 7H), 1.45-1.30 (m, 1H), 1.16 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 490 [M + H]⁺. 857

LCMS (ES, m/z): 488 [M + H]⁺ 858

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.60-7.54 (m, 2H), 7.45-7.40 (m, 1H),7.37-7.30 (m, 3H), 4.78-4.39 (m, 6H), 3.89-3.80 (m, 1H), 3.76 (s, 3H),3.30-3.20 (m, 1H), 3.12-2.80 (m, 1H), 2.75-2.68 (m, 2H), 2.29-2.09 (m,7H), 1.77-1.48 (m, 3H), 1.31-1.28 (m, 1H), 1.20-1.12 (m, 4H). LCMS (ES,m/z): 545 [M + H]+. 859

LCMS (ES, m/z): 493 [M + H]⁺ 860

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.77-7.66 (m, 2H), 7.58-7.56 (m, 1H),7.44 (s, 1H), 6.22-6.20 (m, 1H), 4.86-4.79 (m, 2H), 4.67 (d, J = 7.2 Hz,2H), 4.13-3.95 (m, 2H), 3.79 (s, 3H), 3.50-3.30 (m, 2H), 3.19-2.99 (m,3H), 2.50-2.31 (m, 1H), 2.28-2.15 (m, 2H), 2.03-1.90 (m, 1H), 1.88-1.76(m, 1H), 1.57 (d, J = 7.2 Hz, 3H), 1.56-1.47 (m, 1H), 1.13 (d, J = 6.8Hz, 3H). LCMS (ES, m/z): 486 [M + H]+. 861

LCMS (ES, m/z): 518 [M + H]⁺ 862

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.91 (s, 1H), 7.58 (s, 1H), 7.49-7.34(m, 2H), 6.89-6.51 (m, 1H), 4.81-4.61 (m, 3H), 4.61-4.32 (m, 1H),4.03-3.83 (m, 1H), 3.76 (s, 3H), 3.28-3.12 (m, 1H), 3.02-2.79 (m, 2H),2.49-2.17 (m, 4H), 2.17-2.03 (m, 1H), 1.96-1.81 (m, 2H), 1.80-1.54 (m,3H), 1.38-1.35 (d, J = 6.9 Hz, 3H), 1.13-1.11 (d, J = 6.6 Hz, 3H). LCMS(ES, m/z): 530 [M + H]⁺. 863

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.50-7.35 (m, 2H), 4.86-4.77 (m, 2H),3.94-3.90 (m, 2H), 3.76 (s, 3H), 3.45-3.60 (m, 3H), 2.99-2.86 (m, 4H),2.45-2.18 (m, 6H), 1.91-1.45 (m, 9H), 1.12 (d, J = 6.6 Hz, 3H). LCMS(ES, m/z): 470 [M + H]⁺. 864

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51 (d, J = 8.4 Hz, 1H), 7.41 (d, J =8.8 Hz, 1H), 4.81-4.68 (m, 1H), 4.54-4.40 (m, 1H), 4.06-3.94 (m, 1H),3.78 (s, 3H), 3.53-3.43 (m, 1H), 3.38-3.36 (m, 1H), 3.26-2.97 (m, 3H),2.94-2.83 (m, 1H), 2.69-2.54 (m, 1H), 2.48-2.21 (m, 3H), 2.18-2.01 (m,3H), 1.99-1.80 (m, 4H), 1.79-1.65 (m, 2H), 1.62-1.49 (m, 4H), 1.41-1.26(m, 2H), 1.14 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 484 [M + H]⁺. 865

LCMS (ES, m/z): 497 [M + H]⁺ 866

LCMS (ES, m/z): 477 [M + H]⁺ 867

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.49-7.47 (m, 2H), 7.46 (d, J = 9.2 Hz,1H), 7.29-7.31 (s, 1H), 4.94-4.87 (m, 1H), 4.73-4.68 (m, 1H), 3.76-3.75(s, 6H), 3.55-3.54 (m, 1H), 3.14-3.30 (m, 2H), 2.92-2.79 (m, 3H),2.30-2.24 (m, 4H), 2.23-2.08 (m, 1H), 1.93-1.80 (m, 2H), 1.72-1.64 (m,3H), 1.37-1.39 (d, J = 6.8 Hz, 3H), 1.12-1.34 (d, J = 6.8 Hz, 3H). LCMS(ES, m/z): 494 [M + H]⁺. 868

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.88-7.79 (m, 2H), 7.59-7.50 (m, 4H),6.95-6.57 (m, 1H), 4.88-4.72 (m, 2H), 4.4-4.36 (m, 1H), 4.13-3.92 (m,4H), 3.76 (s, 3H), 3.69-3.60 (m, 2H), 3.11-2.85 (m, 2H), 2.48-2.33 (m,1H), 2.30-2.11 (m, 1H), 1.97-1.78 (m, 3H), 1.67-1.51 (m, 1H), 1.15 (d, J= 6.6 Hz, 3H). LCMS (ES, m/z): 528 [M + H]⁺. 869

¹H NMR (CD₃OD, 300 MHz) δ (ppm): 7.40-7.29 (m, 6H), 7.24-7.22 (m, 1H),4.78-4.75 (m, 1H), 4.43-4.69 (m, 1H), 3.98 (d, J = 10.4 Hz, 1H), 3.75(s, 3H), 3.35-2.28 (m, 1H), 2.96-2.85 (m, 2H), 2.40-2.24 (m, 3H),2.24-1.65 (m, 6H), 1.39-1.36 (m, 1H), 1.17-1.13 (m, 6H), 0.95-0.88 (m,4H). LCMS (ES, m/z): 504 [M + H]⁺. 870

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.86-7.78 (m, 4H), 7.53-7.52 (m, 1H),7.47-7.41 (m, 3H), 7.37-7.34 (m, 1H), 4.87-4.72 (m, 1H), 4.44-4.36 (m,2H), 3.99-3.75 (m, 7H), 3.49-3.43 (m, 2H), 3.32-3.29 (m, 1H), 2.93-2.88(m, 1H), 2.22-2.17 (m, 2H), 1.77-1.73 (m, 1H), 1.47-1.44 (m, 2H), 1.13(d, J = 6.4 Hz, 3H), 1.0-0.9 (m, 1H). LCMS (ES, m/z): 528 [M + H]⁺ 871

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.62-7.49 (m, 3H), 7.41-7.39 (m, 1H),6.57-6.55 (m, 1H), 6.35-6.33 (m, 1H), 4.84-4.75 (m, 2H), 4.54-4.49 (m,2H), 3.78 (s, 3H), 3.56-3.53 (m, 1H), 3.40-3.37 (m, 1H), 3.40-3.37 (m,1H), 3.33-3.32 (m, 1H), 2.91-2.88 (m, 1H), 2.39-2.20 (m, 5H), 1.89-1.64(m, 5H), 1.13 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 493 [M + H]⁺. 872

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.45 (d, J = 9 Hz, 1H), 7.34 (d, J = 9Hz, 1H), 7.24 (d, J = 8.1 Hz, 2H), 7.10 (d, J = 7.8 Hz, 2H), 4.84-4.70(m, 1H), 4.34-3.85 (m, 5H), 3.75 (s, 3H), 3.65-3.45 (m, 2H), 3.35-3.07(m, 2H), 2.90-2.80 (m, 1H), 2.35-2.12 (m, 5H), 1.75-1.60 (m, 3H),1.25-1.18 (m, 1H), 1.12 (d, J = 6.6 Hz, 3H) LCMS (ES, m/z): 492 [M +H]⁺. 873

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.41-7.31 (m, 4H), 7.30-7.15 (m, 3H),4.81-4.65 (m, 3H), 4.30-4.16 (m, 1H), 3.79 (s, 3H), 3.18-3.01 (m, 3H),2.84-2.70 (m, 1H), 2.50-2.39 (m, 1H), 2.38-2.11 (m, 2H), 2.08-1.90 (m,4H), 1.80-1.55 (m, 2H), 1.53-1.35 (m, 2H), 1.16 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 492 [M + H]+. 874

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.13 (d, J = 7.2 Hz, 2H), 7.81-7.55 (m,5H), 5.18-5.01 (m, 1H), , 4.84-4.74 (m, 1H), 3.79 (s, 3H), 3.28-3.11 (m,1H), 3.03-2.92 (m, 2H), 2.62-2.49 (m, 1H), 2.45-2.19 (m, 4H), 2.12-2.01(m, 1H), 1.90-1.62 (m, 4H), 1.16 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):476 [M + H]⁺. 875

LCMS (ES, m/z): 493 [M + H]⁺ 876

LCMS (ES, m/z): 481 [M + H]⁺ 877

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.57-7.47 (m, 2H), 7.40 (s, 1H), 7.36(d, J = 9.2 Hz, 1H), 4.81-4.69 (m, 1H), 4.66-4.56 (m, 1H), 4.53-4.36 (m,2H), 4.01-3.88 (m, 1H), 3.77 (s, 3H), 3.26-3.12 (m, 3H), 3.01-2.88 (m,1H), 2.88-2.70 (m, 2H), 2.48-2.34 (m, 2H), 2.33-2.19 (m, 1H), 1.85-1.78(m, 1H), 1.76-1.63 (m, 1H), 1.50-1.38 (m, 4H), 1.13 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 471 [M + H]⁺. 878

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 6 7.89-7.75 (m, 3H), 7.34 (d, J = 1.6Hz, 1H), 6.27 (t, J = 2.0 Hz, 1H), 5.13-5.02 (m, 1H), 4.85-4.69 (m, 2H),4.21-4.19 (m, 1H), 3.80 (s, 3H), 3.19-3.06 (m, 1H), 3.04-2.91 (m, 2H),2.42-2.32 (m, 2H), 2.30-2.17 (m, 2H), 2.13-2.01 (m, 2H), 1.96-1.78 (m,3H), 1.72-1.57 (m, 4H), 1.34-1.25 (m, 1H), 1.17 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 480 [M + H]⁺. 879

LCMS (ES, m/z): 518 [M + H]⁺ 880

LCMS (ES, m/z): 481 [M + H]⁺ 881

LCMS (ES, m/z): 499 [M + H]⁺ 882

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.71-7.51 (m, 2H), 7.44-7.13 (m, 5H),4.94 (s, 2H), 4.85-4.72 (m, 1H), 3.81 (s, 3H), 3.31-3.01 (m, 3H),2.51-1.76 (m, 7H), 1.71-1.31 (m, 4H), 1.18 (d, J = 6.9 Hz, 3H). LCMS(ES, m/z): 526 [M + H]⁺. 883

LCMS (ES, m/z): 482 [M + H]⁺ 884

LCMS (ES, m/z): 488 [M + H]⁺ 885

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.48 (d, J = 9.2 Hz, 1H), 7.37 (d, J =9.2 Hz, 1H), 7.23-7.15 (m, 2H), 7.14-7.05 (m, 2H), 4.80-4.69 (m, 1H),4.47-4.32 (m, 1H), 4.26-4.14 (m, 1H), 4.08-4.37 (m, 1H), 3.98-3.90 (m,2H), 3.76 (s, 3H), 3.71-3.59 (m, 1H), 3.60-3.44 (m, 1H), 3.35-3.33 (m,1H), 3.23-3.12 (m, 1H), 2.97-2.81 (m, 1H), 2.37-2.14 (m, 5H), 1.80-1.66(m, 3H), 1.27-1.22 (m, 1H), 1.13 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z):492 [M + H]⁺. 886

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52 (d, J = 9.2 Hz, 1H), 7.41 (d, J =9.2 Hz, 1H), 4.82-4.68 (m, 1H), 4.61-4.43 (m, 1H), 4.02-3.84 (m, 2H),3.83-3.71 (m, 4H), 3.25-3.00 (m, 3H), 2.99-2.84 (m, 1H), 2.74-2.55 (m,1H), 2.50-2.24 (m, 3H), 2.23-1.86 (m, 9H), 1.81-1.49 (m, 4H), 1.14 (d, J= 6.4 Hz, 3H). LCMS (ES, m/z): 470 [M + H]⁺. 887

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.34 (s, 1H), 8.20-8.12 (m, 2H),7.58-7.39 (m, 2H), 6.59 (t, J = 6.8 Hz, 1H), 4.80-4.63 (m, 2H), 3.78 (s,3H), 3.21-3.12 (m, 1H), 2.96-2.85 (m, 1H), 2.62-2.37 (m, 3H), 2.29-2.08(m, 4H), 1.99-1.85 (m, 4H), 1.78-1.49 (m, 3H), 1.11 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 494 [M + H]+. 888

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.54-7.35 (m, 2H), 7.31-7.17 (m, 4H),4.85-4.69 (m, 1H), 4.44-4.28 (m, 1H), 4.28-4.17 (m, 1H), 4.09-3.90 (m,2H), 3.78 (s, 3H), 3.73-3.60 (m, 1H), 3.60-3.46 (m, 1H), 3.45-3.35 (m,1H), 3.28-3.11 (m, 1H), 3.01-2.81 (m, 2H), 2.37-2.15 (m, 2H), 1.85-1.66(m, 3H), 1.23 (d, J = 6.9 Hz, 6H), 1.16 (d, J = 6.6 Hz, 3H), 1.11-0.99(m, 1H). LCMS (ES, m/z): 520 [M + H]⁺. 889

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52 (d, J = 8.8 Hz, 1H), 7.42 (d, J =8.8 Hz, 1H), 4.80-4.68 (m, 1H), 4.57-4.42 (m, 1H), 4.03-3.93 (m, 1H),3.79 (s, 3H), 3.56-3.44 (m, 1H), 3.38-3.35 (m, 1H), 3.26-2.98 (m, 3H),2.97-2.83 (m, 1H), 2.73-2.52 (m, 1H), 2.45-2.03 (m, 6H), 2.00-1.81 (m,4H), 1.77-1.53 (m, 6H), 1.40-1.26 (m, 2H), 1.14 (d, J = 6.4 Hz, 3H).LCMS (ES, m/z): 484 [M + H]⁺. 890

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.02-7.72 (m, 2H), 5.16-4.97 (m, 1H),4.81-4.76 (m, 1H), 4.24-4.03 (m, 1H), 3.82 (s, 3H), 3.79-3.69 (m, 1H),3.63-3.42 (m, 4H), 3.13-3.04 (m, 1H), 3.04-2.91 (m, 2H), 2.59-2.39 (m,3H), 2.39-2.19 (m, 4H), 2.19-2.05 (m, 1H), 2.03-1.78 (m, 7H), 1.72-1.56(m, 1H), 1.17 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 497 [M + H]⁺ 891

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.57-7.50 (m, 1H), 7.47-7.34 (m, 6H),4.84-4.68 (m, 2H), 4.42-4.27 (m, 1H), 4.13-3.93 (m, 2H), 3.9-3.76 (m,4H), 3.73-3.60 (m, 1H), 3.29-3.21 (m, 2H), 3.20-3.09 (m, 1H), 3.04-2.86(m, 2H), 2.74-2.59 (m, 1H), 2.31-2.19 (m, 1H), 1.82-1.67 (m, 1H), 1.15(d, J = 5.6 Hz, 3H). LCMS (ES, m/z): 514 [M + H]⁺. 892

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.54 (d, J = 8.4 Hz, 1H), 7.36 (d, J =9.0 Hz, 1H), 4.90-4.76 (m, 1H), 4.74-4.54 (m, 1H), 3.95-3.90 (m, 1H),3.78 (s, 3H), 3.41-3.31 (m, 2H), 3.09-2.87 (m, 3H), 2.80-2.50 (m, 2H),2.50-2.15 (m, 6H), 2.11 (d, J = 3.9 Hz, 3H), 1.98-1.69 (m, 8H),1.42-1.38 (m, 2H), 1.14 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 511 [M +H]⁺ 893

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.50-7.42 (m, 1H), 7.40-7.30 (m, 5H),5.08-4.90 (m, 1H), 4.80-4.70 (m, 1H), 4.35-4.20 (m, 1H), 3.80 (s, 3H),3.78-3.70 (m, 1H), 3.40-3.32 (m, 1H), 3.18-3.05 (m, 1H), 2.92-2.86 (m,1H), 2.40-2.16 (m, 3H), 2.12-1.95 (m, 3H), 1.90-1.65 (m, 4H), 1.13 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 496 [M + H]⁺. 894

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46-7.29 (m, 2H), 7.26 (s, 1H), 7.08(s, 1H), 4.75-4.64 (m, 1H), 4.36-4.12 (m, 1H), 3.76 (s, 3H), 3.73 (s,3H), 3.52-3.39 (m, 1H), 3.26-3.16 (m, 1H), 3.11-2.99 (m, 1H), 2.96-2.84(m, 2H), 2.40-2.04 (m, 6H), 1.88-1.76 (m, 1H), 1.74-1.50 (m, 3H), 1.46(d, J = 6.8 Hz, 3H), 1.32-1.17 (m, 1H), 1.14 (d, J = 6.4 Hz, 3H). LCMS(ES, m/z): 494 [M + H]⁺ 895

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.19-8.03 (m, 2H), 7.86-7.78 (m, 1H),7.78-7.67 (m, 2H), 7.67-7.56 (m, 2H), 5.12-4.96 (m, 1H), 4.87-4.68 (m,1H), 3.79 (s, 3H), 3.29-3.09 (m, 1H), 3.09-2.81 (m, 1H), 2.62-2.43 (m,1H), 2.38-2.03 (m, 5H), 1.89-1.70 (m, 1H), 1.70-1.47 (m, 4H), 1.15 (d, J= 6.6 Hz, 3H). LCMS (ES, m/z): 512 [M + H]⁺. 896

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.93-7.86 (m, 2H), 4.95-4.92 (m, 2H),4.62-4.59 (m, 1H), 3.83 (s, 3H), 3.72-3.65 (m, 3H), 3.55-3.53 (m, 1H),3.08-2.99 (m, 3H), 2.43-2.38 (m, 3H), 2.28-2.24 (m, 2H), 2.126 (m, 1H),1.97-1.56 (m, 11H), 1.17 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 497 [M +H]⁺ 897

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.52 (d, J = 8.4 Hz, 1H), 7.40 (d, J =8.8 Hz, 1H), 4.81-4.68 (m, 1H), 4.57-4.43 (m, 1H), 3.99-3.84 (m, 2H),3.83-3.72 (m, 4H), 3.23-3.00 (m, 3H), 2.97-2.83 (m, 1H), 2.66-2.52 (m,1H), 2.48-2.21 (m, 3H), 2.20-2.02 (m, 4H), 2.01-1.82 (m, 5H), 1.80-1.48(m, 4H), 1.14 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 470 [M + H]⁺. 898

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.92-7.88 (m, 2H), 5.19-5.14 (m, 1H),4.33-4.26 (m, 1H), 3.99-3.97 (m, 1H), 3.83 (s, 3H), 3.73-3.63 (m, 2H),3.45-3.42 (m, 1H), 3.25-2.90 (m, 4H), 2.52-2.47 (m, 2H), 2.32-2.22 (m,5H), 2.11-2.07 (m, 1H), 2.00-1.77 (m, 7H), 1.68-1.59 (m, 4H), 1.18 (d, J= 6.8 Hz, 3H). LCMS (ES, m/z): 511 [M + H]⁺. 899

LCMS (ES, m/z): 511 [M + H]⁺ 900

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51 (d, J = 9.2 Hz, 1H), 7.42-7.27 (m,5H), 4.80-4.69 (m, 1H), 4.51-4.41 (m, 1H), 4.32-4.23 (m, 1H), 4.12-4.02(m, 1H), 4.01-3.89 (m, 2H), 3.76 (s, 3H), 3.73-3.64 (m, 1H), 3.60-3.47(m, 1H), 3.36-3.31 (m, 1H), 3.21-3.08 (m, 1H), 2.96-2.82 (m, 1H),2.43-2.27 (m, 1H), 2.27-2.13 (m, 1H), 1.83-1.65 (m, 3H), 1.49-1.39 (m,1H), 1.12 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 512 [M + H]⁺. 901

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55-7.52 (m, 5H), 7.41 (d, J = 8.8 Hz,1H), 6.92-6.59 (m, 1H), 4.82-4.68 (m, 1H), 4.51-4.25 (m, 2H), 4.15-3.91(m, 3H), 3.78-3.74 (m, 4H), 3.58-3.56 (m, 1H), 3.39-3.37 (m, 1H),3.25-3.08 (m, 1H), 2.96-2.87 (m, 1H), 2.40-2.13 (m, 2H), 1.75-1.69 (m,3H), 1.32-1.28 (m, 1H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 528[M + H]⁺. 902

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.62-7.49 (m, 5H), 7.42 (d, J = 9.2 Hz,1H), 6.96-6.59 (m, 1H), 4.83-4.70 (m, 1H), 4.69-4.52 (m, 1H), 4.47-4.35(m, 1H), 4.07-3.88 (m, 2H), 3.87-3.70 (m, 4H), 3.65-3.54 (m, 1H),3.50-3.41 (m, 1H), 3.40-3.34 (m, 1H), 3.24-3.10 (m, 1H), 2.99-2.85 (m,1H), 2.61-2.44 (m, 1H), 2.29-2.19 (m, 1H), 2.17-2.07 (m, 1H), 2.04-1.82(m, 2H), 1.82-1.66 (m, 1H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):528 [M + H]⁺. 903

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.54-7.52 (m, 1H), 7.50-7.24 (m, 6H),4.86-4.69 (m, 2H), 4.38-4.26 (m, 1H), 4.25-4.13 (m, 1H), 4.12-4.02 (m,1H), 4.01-3.93 (m, 1H), 3.92-3.80 (m, 1H), 3.78 (s, 3H), 3.73-3.58 (m,1H), 3.31-3.26 (m, 1H), 3.25-3.13 (m, 1H), 3.02-2.88 (m, 1H), 2.87-2.66(m, 1H), 2.33-2.14 (m, 1H), 1.96-1.82 (m, 1H), 1.80-1.68 (m, 1H), 1.16(d, J = 6.0 Hz, 3H). LCMS (ES, m/z): 514 [M + H]⁺. 904

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46 (d, J = 8.8 Hz, 1H), 7.38 (d, J =9.2 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 7.02 (d, J = 6.8 Hz, 2H),4.76-4.71 (m, 1H), 4.33-4.31 (m, 1H), 4. 20-4.16 (m, 1H), 4.07-3.87 (m,3H), 3.81 (s, 3H), 3.71-3.69 (m, 1H), 3.69-3.46 (m, 1H), 3.45-3.29 (m,1H), 3.25-3.11 (m, 1H), 2.91-2.87 (m, 1H), 2.27-2.20 (m, 2H), 1.86-1.84(m, 1H), 1.73-1.67 (m, 3H), 1.14-1.12 (m, 4H), 0.93-0.91 (m, 2H),0.63-0.621 (m, 2H). LCMS (ES, m/z): 518 [M + H]⁺. 905

¹H-NMR (DMSO, 300 MHz) δ (ppm): 12.43 (br, 1H), 8.08-7.91 (m, 2H),7.89-7.68 (m, 2H), 7.37-7.16 (m, 6H), 6.89 (d, J = 8.7 Hz, 1H),4.80-4.53 (m, 1H), 4.40-4.20 (m, 1H), 3.62 (s, 3H), 3.47-3.30 (m, 1H),3.14-2.93 (m, 2H), 2.93-2.74 (m, 1H), 2.26-2.04 (m, 1H), 1.73-1.46 (m,1H), 1.04 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 495 [M + H]⁺ 906

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.42 (d, J = 9.2 Hz, 1H), 7.31 (d, J =8.8 Hz, 1H), 7.18-7.00 (m, 3H), 5.08-4.90 (m, 1H), 4.80-4.70 (m, 1H),4.25-4.18 (m, 1H), 3.76 (s, 3H), 3.73-3.67 (m, 1H), 3.36-3.33 (m, 1H),3.14-3.10 (m, 1H), 2.92-2.86 (m, 1H), 2.25-2.16 (m, 6H), 2.08-1.92 (m,3H), 1.90-1.72 (m, 4H), 1.12 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 491[M + H]⁺. 907

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.93-7.79 (m, 3H), 7.38 (s, 1H),4.79-4.46 (m, 2H), 4.46-4.26 (m, 1H), 4.43-4.28 (m, 1H), 3.83 (s, 3H),3.19-3.07 (m, 1H), 3.07-2.92 (m, 1H), 2.71-2.52 (m, 1H), 2.52-2.31 (m,2H), 2.31-2.14 (m, 3H), 2.12-1.99 (m, 1H), 1.99-1.84 (m, 1H), 1.84-1.72(m, 1H), 1.71-1.53 (m, 5H), 1.41-1.26 (m, 1H), 1.21 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 514 [M + H]⁺. 908

¹H-NMR (CD₃OD, 400 MHz).3 (ppm): 7.47-7.43 (m, 2H), 7.40-7.34 (m, 2H),7.28-7.25 (m, 3H), 4.71-4.67 (m, 1H), 4.46-4.34 (m, 1H), 3.76 (s, 3H),3.03-2.97 (m, 1H), 2.75-2.69 (m, 1H), 2.43-2.21 (m, 3H), 2.20-2.16 (m,3H), 2.07-1.99 (m, 2H), 1.69-1.59 (m, 3H), 1.10 (d, J = 6.4 Hz, 3H). MS:(ES, m/z): 464 [M + H]⁺. 909

LCMS (ES, m/z): 481 [M + H]⁺ 910

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.56 (s, 1H), 7.49-7.36 (m, 3H),5.03-4.91 (m, 1H), 4.82-4.69 (m, 1H), 4.66-4.38 (m, 2H), 3.98-3.82 (m,1H), 3.79 (s, 3H), 3.31-3.19 (m, 1H), 3.19-3.12 (m, 3H), 3.01-2.81 (m,3H), 2.64-2.53 (m, 1H), 2.53-2.41 (m, 1H), 2.37-2.20 (m, 1H), 2.20-2.03(m, 2H), 1.83-1.62 (m, 1H), 1.43 (d, J = 6.9 Hz, 3H), 1.40-1.26 (m, 1H),1.16 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 497 [M + H]⁺. 911

LCMS (ES, m/z): 526 [M + H]⁺ 912

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.75 (s, 1H), 7.64 (s, 1H), 7.54-7.23(m, 2H), 6.97-6.38 (m, 1H), 4.79-4.61 (m, 2H), 4.61-4.41 (m, 1H),4.41-4.13 (m, 1H), 4.07-3.89 (m, 1H), 3.76 (s, 3H), 3.28-3.11 (m, 1H),3.07-2.82 (m, 1H), 2.57-2.41 (m, 1H), 2.32-2.08 (m, 4H), 1.92-1.52 (m,5H), 1.44-1.22 (m, 4H), 1.13 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 530[M + H]⁺ 913

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.56-7.31 (m, 2H), 7.27-7.08 (m, 4H),4.83-4.62 (m, 2H), 4.32-4.19 (m, 1H), 4.10-3.91 (m, 2H), 3.88-3.78 (m,4H), 3.71-3.57 (m, 1H), 3.27-3.11 (m, 3H), 3.00-2.80 (m, 2H), 2.72-2.55(m, 1H), 2.32 (s, 3H), 2.27-2.15 (m, 1H), 1.80-1.68 (m, 1H), 1.15 (d, J= 6.0 Hz, 3H). LCMS (ES, m/z): 528 [M + H]⁺. 914

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.93 (d, J = 8.7 Hz, 2H), 7.52-7.33 (m,3H), 7.28-7.04 (m, 5H), 6.88 (d, J = 8.7 Hz, 1H), 4.82-4.68 (m, 1H),4.40-4.16 (m, 1H), 3.75 (s, 3H), 3.65-3.44 (m, 1H), 3.25-3.10 (m, 2H),3.03-2.84 (m, 1H), 2.37-2.16 (m, 1H), 1.83-1.64 (m, 1H), 1.15 (d, J =6.6 Hz, 3H). LCMS (ES, m/z): 495 [M + H]⁺ 915

LCMS (ES, m/z): 481 [M + H]⁺ 916

LCMS (ES, m/z): 481 [M + H]⁺ 917

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.97-7.79 (m, 2H), 7.69 (d, J = 2.4 Hz,1H), 7.42 (d, J = 2.0 Hz, 1H), 6.29-6.27 (m, 1H), 4.76-4.62 (m, 2H),4.58-4.39 (m, 1H), 4.39-4.21 (m, 1H), 3.80 (s, 3H), 3.23-3.07 (m, 1H),3.07-2.85 (m, 1H), 2.64-2.51 (m, 1H), 2.43-2.09 (m, 5H), 2.09-1.97 (m,1H), 1.97-1.83 (m, 1H), 1.81-1.65 (m, 1H), 1.65-1.42 (m, 5H), 1.32-1.21(m, 1H), 1.19 (d, J = 6.8 Hz, 3H). LCMS: (ES, m/z): 480 [M + H]⁺. 918

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53-7.39 (m, 1H), 7.39-7.24 (m, 2H),7.24-7.12 (m, 1H), 4.79-4.66 (m, 1H), 4.66-4.48 (m, 1H), 4.48-4.39 (m,1H), 4.31-4.19 (m, 1H), 4.01-3.81 (m, 1H), 3.76 (s, 3H), 3.29-3.08 (m,1H), 3.02-2.82 (m, 1H), 2.64-2.41 (m, 1H), 2.41-2.01 (m, 5H), 1.95 (s,3H), 1.94-1.79 (m, 1H), 1.79-1.58 (m, 3H), 1.52-1.41 (m, 1H), 1.41 (d, J= 6.9 Hz, 3H), 1.15 (d, J = 6.9 Hz, 3H). LCMS: (ES, m/z): 494 [M + H]⁺.919

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.29 (d, J = 9.0 Hz, 1H), 7.19-7.14 (m,4H), 7.13-7.05 (m, 2H), 4.85-4.71 (m, 1H), 3.75-3.52 (m, 7H), 3.42 (s,2H), 3.32-2.80 (m, 4H), 2.26-1.65 (m, 8H), 1.62-1.50 (m, 4H), 1.15 (d, J= 6.6 Hz, 3H), 0.78-0.60 (m, 1H). LCMS (ES, m/z): 487 [M + H]⁺. 920

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.63-7.51 (m, 5H), 7.44 (d, J = 8.8 Hz,1H), 6.92-6.58 (m, 1H), 4.88-4.84 (m, 1H), 4.83-4.69 (m, 1H), 4.48-4.36(m, 1H), 4.16-4.06 (m, 1H), 4.04-3.95 (m, 1H), 3.94-3.82 (m, 1H), 3.79(s, 3H), 3.76-3.67 (m, 1H), 3.54-3.42 (m, 1H), 3.30-3.25 (m, 1H),3.23-3.12 (m, 1H), 3.00-2.86 (m, 2H), 2.78-2.63 (m, 1H), 2.33-2.16 (m,1H), 1.80-1.67 (m, 1H), 1.14 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 564[M + H]⁺. 921

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.32 (d, J = 8.8 Hz, 1H), 7.19 (d, J =9.2 Hz, 1H), 7.1-6.99 (m, 2H), 6.93-6.82 (m, 1H), 4.82-4.68 (m, 1H),4.32-4.11 (m, 1H), 3.80-3.72 (m, 3H), 3.72-3.65 (m, 2H), 3.62-3.47 (m,3H), 3.31-3.13 (m, 2H), 3.12-3.01 (m, 1H), 2.96-2.84 (m, 1H), 2.35-1.97(m, 5H), 1.82-1.65 (m, 3H), 1.61-1.44 (m, 4H), 1.14 (d, J = 6.8 Hz, 3H),1.02-0.88 (m, 1H). LCMS (ES, m/z): 523 [M + H]⁺. 922

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.59-7.52 (m, 1H), 7.47-7.39 (m, 1H),5.06-4.91 (m, 1H), 4.76-4.65 (m, 1H), 4.44-4.33 (m, 1H), 3.80 (s, 3H),3.39-3.19 (m, 1H), 3.02-2.65 (m, 4H), 2.32-2.05 (m, 5H), 1.92-1.77 (m,3H), 1.76-1.45 (m, 8H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 483[M + H]⁺. 923

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46-7.38 (m, 2H), 5.24-5.19 (m, 1H),4.75-4.69 (m, 1H), 4.68-4.20 (m, 1H), 3.79 (s, 3H), 3.33-3.11 (m, 4H),2.92-2.56 (m, 4H), 2.23-2.13 (m, 1H), 2.09-1.99 (m, 5H), 1.77-1.46 (m,10H), 1.15 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 497 [M + H]⁺. 924

LCMS (ES, m/z): 511 [M + H]⁺ 925

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55 (d, J = 9.6 Hz, 1H), 7.42 (d, J =9.2 Hz, 1H), 5.02-4.89 (m, 1H), 4.72-4.70 (m, 1H), 4.02-3.98 (m, 1H),3.79 (s, 3H), 3.26 (m, 1H), 2.98-2.96 (m, 1H), 2.91-2.71 (m, 3H),2.29-2.12 (m, 3H), 2.14-2.10 (m, 2H), 2.09-1.80 (m, 3H), 1.80-1.62 (m,4H), 1.60-1.25 (m, 6H), 1.15 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 497[M + H]⁺. 926

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.64 (s, 1H), 7.64-7.55 (m, 1H),7.52-7.44 (m, 2H), 5.58-5.45 (m, 1H), 4.90-4.42 (m, 3H), 4.02-3.89 (m,1H), 3.77 (s, 3H), 3.72-3.40 (m, 3H), 3.34-3.18 (m, 2H), 2.98-2.72 (m,2H), 2.39-2.20 (m, 2H), 1.73-1.67 (m, 1H), 1.40 (d, J = 6.9 Hz, 3H),1.13 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 506 [M + H]⁺. 927

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.55-7.36 (m, 2H), 7.28-7.05 (m, 4H),4.83-4.65 (m, 2H), 4.29-4.11 (m, 2H), 4.09-3.90 (m, 2H), 3.91-3.70 (m,4H), 3.69-3.55 (m, 1H), 3.25-3.11 (m, 2H), 3.01-2.85 (m, 1H), 2.79-2.65(m, 1H), 2.37-2.15 (m, 4H), 1.82-1.64 (m, 2H), 1.16 (d, J = 6.0 Hz, 3H).LCMS (ES, m/z): 528 [M + H]⁺. 928

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46 (d, J = 8.8 Hz, 1H), 7.36 (d, J =8.8 Hz, 1H), 7.15 (d, J = 3.2 Hz, 2H), 4.81-4.67 (m, 1H), 4.63-4.49 (m,1H), 3.77 (s, 3H), 3.70 (s, 3H), 3.57-3.37 (m, 3H), 3.27-3.17 (m, 1H),3.17-2.99 (m, 2H), 2.99-2.89 (m, 3H), 2.62-2.44 (m, 2H), 2.33-2.20 (m,1H), 2.00-1.88 (m, 1H), 1.77-1.64 (m, 1H), 1.49 (d, J = 6.8 Hz, 3H),1.17-1.04 (m, 4H) . . . LCMS (ES, m/z): 451 [M + H]⁺ 929

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.54-7.38 (m, 2H), 4.76-4.74 (m, 1H),4.61 (m, 1H), 3.88-3.85 (m, 1H), 3.79-3.70 (m, 4H), 3.66-3.62 (m, 1H),3.37-3.32 (m, 1H), 3.25-3.15 (m, 2H), 2.95-2.90 (m, 1H), 2.65 (m, 1H),2.39-2.26 (m, 5H), 2.20-2.04 (m, 3H), 1.91-1.88 (m, 1H), 1.74-1.66 (m,5H). 1.63-1.58 (m, 2H), 1.44 (d, J = 6.8 Hz, 3H), 1.14 (d, J = 6.8 Hz,3H). LCMS (ES, m/z): 511 [M + H]⁺. 930

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.63-7.41 (m, 4H), 5.60-5.48 (m, 1H),4.88 (s, 1H), 4.79-4.45 (m, 2H), 4.01-3.91 (m, 1H), 3.77 (s, 3H), 3.45(d, J = 9 Hz, 3H), 3.32-3.30 (m, 2H), 2.94-2.92 (m, 2H), 2.65-2.55 (m,1H), 2.32-2.18 (m, 1H), 1.75-1.65 (m, 1H), 1.40 (d, J = 6.9 Hz, 3H),1.13 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 506 [M + H]⁺. 931

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.51 (d, J = 8.8 Hz, 1H), 7.36 (d, J =9.2 Hz, 1H), 7.16-7.02 (m, 2H), 6.95-6.88 (m, 1H), 4.81-4.65 (m, 1H),4.49-4.31 (m, 1H), 3.79 (s, 3H), 3.69-3.57 (m, 1H), 3.33-3.05 (m, 5H),3.00-2.88 (m, 1H), 2.88-2.75 (m, 1H), 2.76-2.65 (m, 1H), 2.53-2.23 (m,3H), 1.81-1.65 (m, 2H), 1.51 (d, J = 6.8 Hz, 3H), 1.15 (d, J = 6.8 Hz,3H), 1.00-0.83 (m, 1H). LCMS (ES, m/z): 483 [M + H]⁺. 932

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.57 (s, 1H), 7.52-7.32 (m, 3H),4.82-4.68 (m, 1H), 4.70-4.54 (m, 2H), 4.53-4.45 (m, 1H), 4.05-3.88 (m,1H), 3.78 (s, 3H), 3.30-3.20 (m, 1H), 3.19-3.00 (m, 3H), 2.98-2.87 (m,2H), 2.57-2.35 (m, 2H), 2.35-2.19 (m, 1H), 2.07-2.01 (m, 1H), 1.98-1.87(m, 1H), 1.85-1.67 (m, 2H), 1.63-1.48 (m, 1H), 1.45 (d, J = 6.8 Hz, 3H),1.16 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 485 [M + H]⁺. 933

LCMS (ES, m/z): 482 [M + H]⁺ 934

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.63-7.59 (m, 2H), 7.41-7.31 (m, 2H),7.22-7.11 (m, 3H), 4.94 (m, 2H), 4.88-4.72 (m, 1H), 3.81 (s, 3H), 3.50(s, 3H), 2.98-2.87 (m, 2H), 2.61-2.51 (m, 2H), 2.28-2.21 (m, 1H),2.19-2.11 (m, 2H), 1.76-1.73 (m, 2H), 1.66-1.63 (m, 1H). 1.58-1.55 (m,2H), 1.18 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z): 505 [M + H]⁺. 935

¹H-NMR (CDCl₃, 300 MHz) δ (ppm): 7.53 (s, 1H), 7.42 (d, J = 8.7 Hz, 1H),7.24 (s, 1H), 7.06 (d, J = 8.7 Hz, 1H), 6.13 (t, J = 2.1 Hz, 1H),4.85-4.76 (m, 1H), 4.72 (t, J = 6.6 Hz, 2H), 3.90 (t, J = 6.6 Hz, 2H),3.78 (s, 3H), 3.45 (t, J = 6.6 Hz, 2H), 3.31-3.16 (m, 1H), 3.08-2.92 (m,1H), 2.90-2.82 (m, 4H), 2.51 (t, J = 6.6 Hz, 2H), 2.48-2.41 (m, 4H),2.31-2.20 (m, 1H), 1.78-1.63 (m, 1H), 1.16 (d, J = 6.6 Hz, 3H). LCMS(ES, m/z): 452 [M + H]⁺. 936

¹H-NMR (DMSO, 400 MHz) δ (ppm): 8.02 (s, 1H), 7.55 (s, 1H), 7.31-7.15(m, 2H), 4.62-455 (m, 1H), 4.54-4.35 (m, 2H), 4.30-4.15 (m, 1H),3.85-3.70 (m, 2H), 3.65 (s, 3H), 3.45-3.35 (m, 2H), 3.35-3.25 (m, 2H),3.12-3.01 (m, 1H), 2.85-2.75 (m, 1H), 2.20-1.90 (m, 5H), 1.80-1.46 (m,5H), 1.18 (d, J = 6.8 Hz, 3H), 1.06 (d, J = 6.4 Hz, 3H). LCMS (ES, m/z):511 [M + H]⁺. 937

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.60-7.47 (m, 5H), 7.43 (d, J = 9.2 Hz,1H), 6.90-6.56 (m, 1H), 4.88-4.81 (m, 1H), 4.80-4.71 (m, 1H), 4.38-4.28(m, 1H), 4.25-4.14 (m, 1H), 4.13-4.07 (m, 1H), 4.03-3.93 (m, 1H),3.94-3.80 (m, 1H), 3.78 (s, 3H), 3.73-3.63 (m, 1H), 3.32-3.26 (m, 1H),3.24-3.12 (m, 1H), 2.98-2.87 (m, 1H), 2.86-2.70 (m, 1H), 2.34-2.17 (m,1H), 2.00-1.89 (m, 1H), 1.84-1.69 (m, 1H), 1.15 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 564 [M + H]⁺. 938

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.63 (s, 1H), 7.51-7.34 (m, 3H),4.82-4.73 (m, 1H), 4.72-4.59 (m, 2H), 4.58-4.44 (m, 1H), 4.05-3.88 (m,1H), 3.79 (s, 3H), 3.55-3.34 (m, 3H), 3.30-3.16 (m, 2H), 3.01-2.87 (m,1H), 2.75-2.59 (m, 1H), 2.54-2.42 (m, 1H), 2.36-2.23 (m, 1H), 2.21-1.95(m, 3H), 1.88-1.67 (m, 2H), 1.44 (d, J = 6.8 Hz, 3H), 1.15 (d, J = 6.4Hz, 3H). LCMS (ES, m/z): 485 [M + H]⁺. 939

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.53-7.46 (m, 2H), 4.98-4.89 (m, 1H),4.78-4.73 (m, 2H), 3.80 (s, 3H), 3.27-3.21 (m, 1H), 3.15 (s, 3H),3.05-2.92 (m, 1H), 2.92-2.70 (m, 3H), 2.30-2.15 (m, 3H), 1.98-1.81 (m,5H), 1.80-1.52 (m, 7H), 1.52-1.40 (m, 2H), 1.31-1.20 (m, 1H), 1.15 (d, J= 6.4 Hz, 3H). LCMS (ES, m/z): 511 [M + H]⁺. 940

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.61 (s, 1H), 7.54-7.51 (m, 2H), 7.43(s, 1H), 5.05-4.95 (m, 2H), 4.85-4.70 (m, 1H), 4.58-4.45 (m, 2H),4.00-3.85 (m, 1H), 3.75 (s, 3H), 3.25-3.10 (m, 4H), 2.98-2.88 (m, 1H),2.75-2.55 (m, 3H), 2.30-2.15 (m, 2H), 2.05-1.95 (m, 4H), 1.80-1.70 (m,1H), 1.43 (d, J = 7.2 Hz, 3H), 1.14 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):511 [M + H]⁺. 941

LCMS (ES, m/z): 482 [M + H]⁺ 942

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.41-7.24 (m, 2H), 7.20-7.03 (m, 5H),4.79-4.64 (m, 1H), 4.46-4.42 (m, 1H), 3.76 (s, 3H), 3.62-3.49 (m, 1H),3.31-3.15 (m, 2H), 3.12-3.01 (m, 2H), 2.99-2.78 (m, 3H), 2.71-2.68 (m,1H), 2.46-2.36 (m, 1H), 2.34-2.12 (m, 2H), 1.95-1.79 (m, 2H), 1.79-1.61(m, 2H), 1.49 (d, J = 6.8 Hz, 3H), 1.16 (d, J = 6.8 Hz, 3H), 1.02-0.98(m, 1H). LCMS (ES, m/z): 461 [M + H]⁺. 943

LCMS (ES, m/z): 478 [M + H]⁺ 944

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.56 (s, 1H), 7.43 (s, 1H), 7.42-7.36(m, 2H), 5.16-5.05 (m, 1H), 4.80-4.70 (m, 1H), 4.70-4.59 (m, 1H),4.55-4.44 (m, 1H), 4.05-3.89 (m, 1H), 3.79 (s, 3H), 3.45-3.35 (m, 1H),3.29-3.07 (m, 4H), 3.01-2.87 (m, 1H), 2.41-2.20 (m, 3H), 1.80-1.64 (m,1H), 1.41 (d, J = 6.9 Hz, 3H), 1.13 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z):457 [M + H]⁺. 945

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.77-7.56 (m, 3H), 7.44 (s, 1H), 6.22(t, J = 2.0 Hz, 1H), 4.99-4.92 (m, 1H), 4.83-4.79 (m, 1H), 4.67 (d, J =6.0 Hz, 2H), 4.13-4.01 (m, 1H), 3.99-3.89 (m, 1H), 3.79 (s, 3H),3.50-3.30 (m, 1H), 3.19-2.99 (m, 3H), 2.80-2.45 (m, 2H), 2.35-2.01 (m,4H), 1.90-1.75 (m, 1H), 1.57 (d, J = 6.8 Hz, 3H), 1.13 (d, J = 6.8 Hz,3H). LCMS (ES, m/z): 486 [M + H]⁺. 946

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.61 (d, J = 2.0 Hz, 1H), 7.44 (d, J =2.0 Hz, 1H), 7.40 (m, 2H), 6.14-6.13 (m, 1H), 4.80-4.60 (m, 3H),4.55-4.45 (m, 1H), 4.02-3.89 (m, 1H), 3.79 (s, 3H), 3.80-3.35 (m, 2H),3.28-2.99 (m, 4H), 2.95-2.81 (m, 2H), 2.31-2.11 (m, 2H), 1.65-1.55 (m,2H), 1.43 (d, J = 7.2 Hz, 3H), 1.13 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z):486 [M + H]⁺. 947

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.46 (d, J = 8.8 Hz, 1H), 7.33 (d, J =9.2 Hz, 1H), 7.19-7.06 (m, 5H), 4.81-4.68 (m, 1H), 4.31-4.20 (m, 1H),3.78 (s, 3H), 3.70-3.56 (m, 1H), 3.28-3.20 (m, 1H), 3.20-3.02 (m, 3H),3.02-2.88 (m, 2H), 2.80-2.71 (m, 1H), 2.59-2.47 (m, 1H), 2.41-2.30 (m,1H), 2.30-2.21 (m, 1H), 2.21-1.99 (m, 1H), 1.81-1.68 (m, 2H), 1.53 (d, J= 6.8 Hz, 3H), 1.15 (d, J = 6.8 Hz, 3H), 0.70-0.56 (m, 1H). LCMS (ES,m/z): 447 [M + H]⁺. 948

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 8.02 (d, J = 8.4 Hz, 2H), 7.65-7.56 (m,2H), 7.41-7.36 (m, 2H), 7.10-7.06 (m, 1H), 4.88 (m, 1H), 4.80-4.74 (m,1H), 3.81 (s, 3H), 3.34-3.26 (m, 1H), 3.06-2.76 (m, 4H), 2.27-2.19 (m,3H), 1.90-1.60 (m, 5H), 1.17 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 491[M + H]⁺. 949

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53-7.24 (m, 4H), 5.55-5.38 (m, 1H),4.82-4.65 (m, 1H), 4.55-4.28 (m, 2H), 4.13-3.75 (m, 4H), 3.50-3.20 (m,5H), 3.18-2.78 (m, 2H), 2.62-2.48 (m, 1H), 2.28-2.16 (m, 1H), 2.08-2.00(m, 1H), 1.98 (s, 2H), 1.75-1.58 (m, 1H), 1.41 (d, J = 6.9 Hz, 2H),1.32-1.26 (m, 1H), 1.12 (d, J = 6.6 Hz, 2H). LCMS (ES, m/z): 486 [M +H]⁺. 950

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 8.28-7.93 (m, 1H), 7.62-7.32 (m, 3H),5.10-4.99 (m, 1H), 4.81-4.62 (m, 2H), 4.53-4.45 (m, 1H), 4.05-3.86 (m,1H), 3.75 (s, 3H), 3.65-3.52 (m, 3H), 3.26-2.83 (m, 3H), 2.31-1.97 (m,3H), 1.71-1.56 (m, 1H), 1.43 (d, J = 6.9 Hz, 3H), 1.07 (d, J = 6.9 Hz,3H). LCMS (ES, m/z): 457 [M + H]+. 951

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.47 (d, J = 9.2 Hz, 1H), 7.36 (d, J =8.8 Hz, 1H), 7.24 (s, 1H), 7.14 (s, 1H), 4.80-4.67 (m, 1H), 4.62-4.43(m, 1H), 3.76 (s, 3H), 3.72 (s, 3H), 3.55-3.45 (m, 1H), 3.43-3.33 (m,2H), 3.28-3.20 (m, 1H), 3.13-2.97 (m, 2H), 2.97-2.84 (m, 3H), 2.67-2.35(m, 2H), 2.35-2.16 (m, 1H), 1.94-1.84 (m, 1H), 1.76-1.65 (m, 1H), 1.47(d, J = 6.8 Hz, 3H), 1.26-1.08 (m, 4H). LCMS (ES, m/z): 451 [M + H]⁺ 952

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.60 (s, 1H), 7.53 (d, J = 9.2 Hz, 1H),7.43 (s, 1H), 7.36 (d, J = 9.2 Hz, 1H), 4.79-4.69 (m, 1H), 4.67-4.54 (m,1H), 4.52-4.36 (m, 2H), 4.01-3.88 (m, 1H), 3.76 (s, 3H), 3.29-3.15 (m,3H), 2.98-2.69 (m, 3H), 2.53-2.19 (m, 3H), 1.85-1.76 (m, 1H), 1.77-1.65(m, 1H), 1.51-1.41 (m, 1H), 1.40 (d, J = 6.8 Hz, 3H), 1.13 (d, J = 6.4Hz, 3H). LCMS (ES, m/z): 471 [M + H]⁺. 953

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.38-7.25 (m, 2H), 7.21-7.00 (m, 5H),4.78-4.67 (m, 1H), 4.43-4.39 (m, 1H), 3.75 (s, 3H), 3.65-3.51 (m, 1H),3.31-3.18 (m, 1H), 3.18-3.12 (m, 1H), 3.11-2.98 (m, 4H), 2.98-2.75 (m,2H), 2.44-2.32 (m, 1H), 2.32-2.18 (m, 2H), 2.03-1.99 (m, 1H), 1.78-1.59(m, 2H), 1.54 (d, J = 6.8 Hz, 3H), 1.50-1.35 (m, 1H), 1.16 (d, J = 6.4Hz, 3H), 0.91-0.86 (m, 1H). LCMS (ES, m/z): 461 [M + H]⁺. 954

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.82-7.62 (m, 3H), 7.44 (s, 1H), 6.22(t, J = 2.4 Hz, 1H), 4.86-4.67 (m, 4H), 4.13-3.95 (m, 2H), 3.79 (s, 3H),3.50-3.30 (m, 2H), 3.19-2.99 (m, 3H), 2.50-2.31 (m, 1H), 2.28-2.15 (m,2H), 2.03-1.79 (m, 2H), 1.57 (d, J = 6.8 Hz, 3H), 1.56-1.47 (m, 1H),1.13 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 486 [M + H]⁺. 955

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.86 (s, 2H), 7.70 (s, 1H), 7.42 (s,1H), 6.33-6.28 (m, 1H), 5.82-5.60 (m, 1H), 4.92-4.65 (m, 3H), 4.35-4.22(m, 1H), 3.82-3.75 (m, 4H), 3.72-3.42 (m, 2H), 3.25-2.92 (m, 3H),2.85-2.65 (m, 1H), 2.35-2.14 (m, 2H), 1.98-1.85 (m, 1H), 1.61 (d, J =7.2 Hz, 3H), 1.18 (d, J = 6.6 Hz, 3H). LCMS (ES, m/z): 472 [M + H]⁺. 956

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.53-7.40 (m, 4H), 6.19-6.17 (m, 1H),5.55-5.38 (m, 1H), 4.80-4.45 (m, 3H), 3.98-3.85 (m, 1H), 3.75 (s, 3H),3.54-3.10 (m, 5H), 2.95-2.78 (m, 2H), 2.62-2.48 (m, 1H), 2.28-2.15 (m,1H), 1.75-1.68 (m, 1H), 1.43 (d, J = 6.9 Hz, 3H), 1.13 (d, J = 6.9 Hz,3H). LCMS (ES, m/z): 472 [M + H]⁺. 957

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.24 (d, J = 8.8 Hz, 1H), 6.99 (d, J =8.8 Hz, 1H), 6.93-6.84 (m, 2H), 6.66-6.62 (m, 1H), 4.74-4.61 (m, 1H),4.52-4.39 (m, 1H), 3.86 (s, 3H), 3.79 (s, 3H), 3.05-2.99 (m, 1H),2.85-2.70 (m, 2H), 2.69-2.58 (m, 1H), 2.55-2.45 (m, 1H), 2.41-2.32 (m,1H), 2.31-2.20 (m, 1H), 2.18-2.07 (m, 1H), 1.86-1.60 (m, 7H), 1.52-1.35(m, 1H), 1.06 (d, J = 6.8 Hz, 3H). LCMS (ES, m/z): 540 [M + H]⁺. 958

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.85 (s, 2H), 7.49 (s, 1H), 7.23 (s,1H), 5.78-5.62 (m, 1H), 4.91-4.53 (m, 3H), 4.28-4.15 (m, 1H), 3.84-3.40(m, 6H), 3.32-2.94 (m, 3H), 2.86-2.68 (m, 1H), 2.35-2.14 (m, 2H), 2.00(s, 3H), 1.95-1.84 (m, 1H), 1.58 (d, J = 6.6 Hz, 3) 1.28 (d, J = 6.6 Hz,3H). LCMS (ES, m/z): 486 [M + H]⁺. 959

¹H-NMR (CD₃OD, 300 MHz) δ (ppm): 7.56 (s, 1H), 7.52-7.32 (m, 3H),5.04-4.92 (m, 1H), 4.83-4.69 (m, 1H), 4.68-4.52 (m, 1H), 4.52-4.37 (m,1H), 4.01-3.82 (m, 1H), 3.79 (s, 3H), 3.31-3.15 (m, 2H), 3.15-3.09 (m,2H), 3.09-2.82 (m, 4H), 2.72-2.56 (m, 1H), 2.56-2.38 (m, 1H), 2.37-2.21(m, 1H), 2.18-1.98 (m, 2H), 1.85-1.68 (m, 1H), 1.42 (d, J = 6.9 Hz, 3H),1.17 (d, J = 6.9 Hz, 3H). LCMS (ES, m/z): 497 [M + H]⁺. 960

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 6.95-6.81 (m, 4H), 6.68-6.65 (m, 1H),4.74-4.61 (m, 1H), 4.52-4.39 (m, 1H), 3.86 (s, 3H), 3.79 (s, 3H),2.95-2.60 (m, 4H), 2.49-2.35 (m, 1H), 2.21-2.05 (m, 3H), 1.96-1.85 (m,2H), 1.80 (s, 3H), 1.72-1.55 (m, 3H), 0.95 (d, J = 6.8 Hz, 3H). LCMS(ES, m/z): 540 [M + H]⁺. 961

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 9.06-9.04 (m, 1H), 7.71-7.63 (m, 2H),7.51-7.48 (m, 1H), 7.44-7.39 (m, 1H), 7.10-7.05 (m, 1H), 5.07-5.01 (m,1H), 4.88-4.76 (m, 1H), 3.82 (s, 3H), 3.34-3.26 (m, 1H), 3.09-2.76 (m,4H), 2.28-2.20 (m, 3H), 1.91-1.60 (m, 5H), 1.17 (d, J = 6.8 Hz, 3H).LCMS (ES, m/z): 525 [M + H]⁺. 962

¹H-NMR (CD₃OD, 400 MHz) δ (ppm): 7.75 (s, 1H), 7.45-7.32 (m, 3H),7.19-7.15 (m, 2H), 6.43 (s, 1H), 6.42 (s, 1H), 5.04-4.91 (m, 1H),4.80-4.79 (m, 1H), 3.79 (s, 3H), 3.78 (s, 3H), 3.31-3.22 (m, 1H),3.11-3.00 (m, 1H), 2.91-2.85 (m, 1H), 2.45-2.31 (m, 2H), 2.28-2.21 (m,1H), 2.12-2.00 (m, 1H), 1.91-1.70 (m, 2H), 1.55-1.30 (m, 2H), 1.25-1.18(m, 1H), 1.16 (d, J = 6.8 Hz, 3H), 0.82-0.78 (m, 1H). LCMS (ES, m/z):531 [M + H]⁺.

Example 963: HTRF Biochemical Assay for CBP and BRD4 Activity

The assay was performed in a final volume of 6 μL in assay buffercontaining 50 mM Hepes (pH 7.5, (0.5M Hepes, pH 7.5 solution; TeknovaH1575)), 0.5 mM GSH, 0.01% BGG (0.22 μM filtered, Sigma, G7516-25G),0.005% BSA (0.22 μM filtered, EMD Millipore Cosporation, 126575) and0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point,3-fold serial dilution in DMSO were pre-dispensed into 1536 assay plates(Corning, #3724BC) for a final test concentration of 33 μM to 1.7 nM,top to lowest dose, respectively. 3 μL of 2× Protein and 3 μL of 2×Peptide Ligand were added to assay plates (pre-stamped with compound).Plates were incubated for varying times at room temperature prior tomeasuring the signal. TR-FRET (Time-Resolved Fluorescence ResonanceEnergy Transfer) was measured on the PHERAstar (BMG, equipped with HTRFoptic module [337/520/490]) or on the Envision (PerkinElmer, equippedwith the TRF Laser unit, TRF dual mirror D400/D505 and emission filtersM520 and M495). Data were reported as percent inhibition compared withcontrol wells based on the following equation: % inh=1−((TR-FRETratio−AveLow)/(AveHigh−AveLow)) where TR-FRET ratio=(Fluorescence at 520nm/Fluorescence at 490 nm)*10000), AveLow=average TR-FRET ratio of noenzyme control (n=32), and AveHigh=average TR-FRET ratio of DMSO control(n=32). IC50 values were determined by curve fitting of the standard 4parameter logistic fitting algorithm included in the Activity Basesoftware package: IDBS XE Designer Model205. Data is fitted using theLevenburg Marquardt algorithm. For all assay formats data were reportedas percent inhibition compared with control wells based on the followingequation: % inh=100*((FLU−AveLow)/(AveHigh−AveLow)) where FLU=measuredFluorescence, AveLow=average Fluorescence of no enzyme control (n=32),and AveHigh=average Fluorescence of DMSO control (n=32). IC50 valueswere determined by curve fitting of the standard 4 parameter logisticfitting algorithm included in the Activity Base software package: IDBSXE Designer Model205. Data is fitted using the Levenburg Marquardtalgorithm. IC₅₀ values are shown in Table 19, below. As set forth inTable 19 below, an IC₅₀ value of greater than or equal to 0.001 μM andless than or equal to 0.01 M is marked “++++”; a value greater than 0.01μM and less than or equal to 0.1 μM is marked “+++”; a value greaterthan 0.1 μM and less than or equal to 1 μM is marked “++”; and a valuegreater than 1 μM and less than 1000 μM is marked “+.” Compounds thatwere not tested in a particular assay are marked “NT.”

TABLE 19 IC₅₀ Values Example No. CBP IC₅₀ (μM gmean) BRD4 IC₅₀ (μMgmean) 1 + + 2 ++ + 3 ++ + 4 + + 5 + + 6 ++ + 7 ++ + 8 ++ NT 9 + +10 + + 11 + + 12 + + 13 + + 14 + + 15 + + 16 ++++ + 17 +++ + 18 ++ + 19+++ + 20 ++ + 21 ++ + 22 ++ + 23 +++ + 24 +++ + 25 +++ + 26 ++ + 27++++ + 28 ++++ + 29 +++ + 30 ++ + 31 +++ + 32 ++ + 33 ++ + 34 ++ + 35++ + 36 +++ + 37 +++ + 38 ++ + 39 +++ + 40 +++ + 41 +++ + 42 +++ + 43+++ + 44 ++ + 45 ++ + 46 +++ + 47 ++ + 48 ++ + 49 ++ + 50 ++ + 51 ++ +52 +++ + 53 +++ + 54 +++ + 55 ++ + 56 +++ + 57 +++ + 58 ++ + 59 ++ + 60++++ + 61 +++ + 62 +++ + 63 ++ + 64 ++++ + 65 +++ + 66 +++ + 67 ++ + 68++ ++ 69 +++ + 70 ++ + 71 ++ + 72 +++ + 73 +++ + 74 +++ + 75 +++ ++ 76++++ ++ 77 +++ + 78 + + 79 ++ + 80 ++ + 81 +++ + 82 +++ + 83 ++ + 84++ + 85 ++ + 86 + + 87 + + 88 ++ + 89 + + 90 ++ + 91 ++ + 92 +++ ++ 93++ + 94 +++ + 95 +++ + 96 +++ + 97 ++ + 98 ++ + 99 ++ + 100 ++ + 101++ + 102 ++ + 103 +++ + 104 ++ + 105 +++ + 106 + + 107 ++ + 108 +++ +109 +++ + 110 +++ + 111 + + 112 ++ + 113 ++ + 114 + + 115 + + 116 ++ +117 + + 118 ++ + 119 ++ + 120 ++ + 121 ++ + 122 ++ + 123 ++ + 124 ++ +125 ++ + 126 ++ + 127 +++ ++ 128 ++ + 129 +++ + 130 ++ + 131 +++ +132 + + 133 ++ + 134 + + 135 ++ + 136 + + 137 + + 138 +++ + 139 ++ + 140++++ ++ 141 ++++ + 142 +++ + 143 ++++ + 144 +++ + 145 +++ + 146 ++ + 147++ + 148 ++ + 149 +++ + 150 + + 151 +++ + 152 +++ + 153 +++ + 154 +++ +155 ++++ + 156 +++ + 157 ++ + 158 ++++ + 159 +++ + 160 ++++ + 161 ++++ +162 +++ + 163 ++++ + 164 ++++ + 165 +++ + 166 +++ + 167 ++++ + 168 +++ +169 ++++ + 170 +++ + 171 ++++ + 172 +++ + 173 ++++ + 174 +++ + 175++++ + 176 ++++ + 177 +++ + 178 ++++ + 179 ++++ + 180 +++ + 181 ++++ +182 +++ + 183 ++++ + 184 +++ + 185 +++ + 186 ++++ + 187 ++++ + 188 +++NT 189 ++++ + 190 +++ + 191 ++++ + 192 ++ + 193 +++ + 194 +++ + 195 ++ +196 +++ + 197 ++ + 198 + + 199 +++ + 200 ++++ + 201 +++ + 202 ++++ + 203+++ + 204 ++++ + 205 +++ + 206 ++ + 207 ++++ + 208 +++ + 209 +++ + 210+++ + 211 ++++ + 212 +++ + 213 ++++ + 214 ++++ + 215 +++ + 216 ++ + 217++ + 218 ++ + 219 ++ + 220 ++ + 221 ++ + 222 ++ + 223 +++ + 224 ++ + 225++ + 226 ++ + 227 ++ + 228 ++ + 229 + + 230 + + 231 + + 232 + + 233 + +234 ++ + 235 ++ + 236 ++ + 237 ++ + 238 ++ + 239 ++ + 240 ++ + 241 +++ +242 ++ + 243 ++ + 244 +++ + 245 +++ + 246 ++ + 247 + + 248 + + 249 + +250 + + 251 + + 252 + ++ 253 ++ + 254 +++ + 255 +++ + 256 +++ + 257+++ + 258 ++ + 259 ++ + 260 ++ + 261 ++ + 262 ++ + 263 +++ + 264 +++ +265 +++ + 266 ++ + 267 ++ + 268 ++ + 269 ++ + 270 ++ + 271 + + 272 ++ +273 ++ + 274 ++ + 275 ++ + 276 +++ + 277 +++ + 278 +++ + 279 ++ + 280++++ + 281 ++ + 282 ++ + 283 ++++ + 284 ++ + 285 ++ + 286 ++ + 287 ++ +288 ++ + 289 ++ + 290 + + 291 ++ NT 292 ++ + 293 + + 294 ++ + 295 + +296 + + 297 + + 298 ++ + 299 ++ + 300 + + 301 ++ + 302 ++ + 303 ++ + 304++ + 305 ++ + 306 + + 307 + + 308 ++ + 309 ++ + 310 ++ + 311 + + 312++ + 313 ++ + 314 ++ + 315 + + 316 + + 317 ++ + 318 ++ + 319 + + 320++ + 321 + + 322 ++ + 323 ++ + 324 ++ + 325 ++ + 326 ++ + 327 ++ +328 + + 329 ++ + 330 + + 331 + + 332 ++ + 333 ++ + 334 + + 335 ++ +336 + + 337 ++ + 338 + + 339 ++ + 340 ++ + 341 ++ + 342 ++ + 343 + + 344++ + 345 ++ + 346 ++ + 347 ++ + 348 ++ + 349 + + 350 ++ + 351 ++ + 352++ + 353 ++ + 354 + + 355 + + 356 ++ + 357 ++ + 358 ++ + 359 ++ + 360++ + 361 ++ + 362 ++ + 363 ++ + 364 ++ + 365 ++ + 366 ++ + 367 ++ +368 + + 369 ++ + 370 ++ + 371 ++ + 372 ++ + 373 + + 374 ++ + 375 + + 376++ + 377 +++ + 378 + + 379 ++ + 380 ++ + 381 ++ + 382 + + 383 +++ + 384++ + 385 ++ + 386 +++ + 387 ++ + 388 ++++ + 389 ++++ + 390 ++ + 391 + +392 ++++ + 393 ++ + 394 +++ + 395 ++ + 396 ++ + 397 ++ + 398 ++ +399 + + 400 ++ + 401 ++ + 402 ++ + 403 + + 404 ++++ + 405 ++++ + 406++++ + 407 ++++ + 408 ++++ + 409 ++++ ++ 410 ++++ ++ 411 ++++ ++ 412++++ ++ 413 ++++ ++ 414 ++++ ++ 415 ++++ ++ 416 ++++ ++ 417 ++++ ++ 418++++ ++ 419 ++++ ++ 420 ++++ ++ 421 ++++ ++ 422 ++++ ++ 423 ++++ ++ 424++++ ++ 425 ++++ ++ 426 ++++ ++ 427 ++++ ++ 428 ++++ ++ 429 ++++ ++ 430++++ ++ 431 ++++ ++ 432 ++++ + 433 ++++ ++ 434 ++++ ++ 435 ++++ ++ 436++++ ++ 437 ++++ ++ 438 ++++ ++ 439 ++++ ++ 440 ++++ ++ 441 ++++ ++ 442++++ ++ 443 ++++ + 444 ++++ ++ 445 ++++ ++ 446 ++++ + 447 ++++ + 448++++ ++ 449 ++++ + 450 ++++ ++ 451 ++++ ++ 452 ++++ ++ 453 ++++ +++ 454++++ ++ 455 ++++ + 456 ++++ + 457 ++++ ++ 458 ++++ ++ 459 ++++ + 460++++ ++ 461 ++++ ++ 462 ++++ + 463 ++++ + 464 ++++ ++ 465 ++++ ++ 466++++ + 467 ++++ ++ 468 ++++ + 469 ++++ +++ 470 ++++ ++ 471 ++++ + 472++++ ++ 473 ++++ ++ 474 ++++ ++ 475 ++++ + 476 ++++ ++ 477 ++++ + 478++++ ++ 479 ++++ + 480 ++++ ++ 481 ++++ + 482 ++++ ++ 483 ++++ ++ 484++++ ++ 485 ++++ + 486 ++++ ++ 487 ++++ ++ 488 ++++ ++ 489 ++++ + 490++++ + 491 ++++ ++ 492 ++++ + 493 ++++ ++ 494 ++++ ++ 495 ++++ + 496++++ ++ 497 ++++ + 498 ++++ ++ 499 ++++ ++ 500 ++++ ++ 501 ++++ ++ 502++++ + 503 ++++ ++ 504 ++++ + 505 ++++ + 506 ++++ + 507 ++++ ++ 508++++ + 509 ++++ + 510 ++++ + 511 ++++ + 512 ++++ + 513 ++++ + 514 ++++ +515 ++++ ++ 516 ++++ + 517 ++++ ++ 518 ++++ ++ 519 ++++ ++ 520 ++++ ++521 ++++ + 522 ++++ + 523 ++++ ++ 524 ++++ + 525 ++++ ++ 526 ++++ + 527++++ ++ 528 ++++ ++ 529 ++++ + 530 ++++ ++ 531 ++++ ++ 532 ++++ + 533++++ + 534 ++++ + 535 ++++ ++ 536 ++++ + 537 ++++ ++ 538 ++++ + 539++++ + 540 ++++ ++ 541 ++++ + 542 ++++ + 543 ++++ ++ 544 ++++ + 545 ++++++ 546 ++++ + 547 ++++ ++ 548 ++++ ++ 549 ++++ + 550 ++++ + 551 ++++ +552 ++++ ++ 553 ++++ + 554 ++++ ++ 555 ++++ + 556 ++++ ++ 557 ++++ ++558 ++++ + 559 ++++ + 560 ++++ + 561 ++++ + 562 ++++ + 563 ++++ + 564++++ + 565 ++++ + 566 ++++ ++ 567 ++++ ++ 568 ++++ + 569 ++++ ++ 570++++ ++ 571 ++++ ++ 572 ++++ + 573 ++++ ++ 574 ++++ + 575 ++++ + 576++++ ++ 577 ++++ + 578 ++++ + 579 ++++ ++ 580 ++++ + 581 ++++ + 582++++ + 583 ++++ + 584 ++++ + 585 ++++ ++ 586 ++++ ++ 587 ++++ ++ 588++++ + 589 ++++ + 590 ++++ + 591 ++++ + 592 ++++ ++ 593 ++++ + 594++++ + 595 ++++ ++ 596 ++++ + 597 ++++ + 598 ++++ ++ 599 ++++ ++ 600 +++++ 601 +++ + 602 +++ + 603 +++ + 604 +++ ++ 605 +++ ++ 606 +++ +++ 607+++ + 608 +++ +++ 609 +++ ++ 610 +++ + 611 +++ + 612 +++ ++ 613 +++ +614 +++ + 615 +++ + 616 +++ + 617 +++ + 618 +++ ++ 619 +++ + 620 +++ +621 +++ + 622 +++ + 623 +++ ++ 624 +++ ++ 625 +++ + 626 +++ ++ 627 +++ +628 +++ + 629 +++ + 630 +++ ++ 631 +++ + 632 +++ + 633 +++ + 634 +++ +635 +++ ++ 636 +++ + 637 +++ + 638 +++ + 639 +++ + 640 +++ ++ 641 +++ +642 +++ ++ 643 +++ + 644 +++ + 645 +++ + 646 +++ + 647 +++ ++ 648 +++ +649 +++ + 650 +++ + 651 +++ + 652 +++ ++ 653 +++ ++ 654 +++ + 655 +++ +656 +++ + 657 +++ + 658 +++ ++ 659 +++ + 660 +++ + 661 +++ + 662 +++ ++663 +++ + 664 +++ + 665 +++ + 666 +++ ++ 667 +++ ++ 668 +++ + 669 +++ +670 +++ ++ 671 +++ + 672 +++ ++ 673 +++ + 674 +++ + 675 +++ + 676 +++ +677 +++ ++ 678 +++ ++ 679 +++ + 680 +++ + 681 +++ + 682 +++ + 683 +++ ++684 +++ ++ 685 +++ ++ 686 +++ ++ 687 +++ + 688 +++ + 689 +++ ++ 690 +++++ 691 +++ + 692 +++ + 693 +++ ++ 694 +++ ++ 695 +++ + 696 +++ + 697+++ + 698 +++ + 699 +++ + 700 +++ + 701 +++ + 702 +++ + 703 +++ ++ 704+++ + 705 +++ ++ 706 +++ + 707 +++ + 708 +++ + 709 +++ + 710 +++ + 711+++ + 712 +++ + 713 +++ + 714 +++ + 715 +++ ++ 716 +++ ++ 717 +++ + 718+++ + 719 +++ ++ 720 +++ + 721 +++ + 722 +++ ++ 723 +++ + 724 +++ + 725+++ + 726 +++ + 727 +++ ++ 728 +++ + 729 +++ + 730 +++ + 731 +++ + 732+++ + 733 +++ + 734 +++ + 735 +++ + 736 +++ ++ 737 +++ + 738 +++ + 739+++ ++ 740 +++ + 741 +++ + 742 +++ + 743 +++ + 744 +++ + 745 +++ + 746+++ ++ 747 +++ + 748 +++ + 749 +++ + 750 +++ 751 +++ + 752 +++ + 753+++ + 754 +++ + 755 +++ + 756 +++ + 757 +++ + 758 +++ + 759 +++ + 760+++ + 761 +++ ++ 762 +++ + 763 +++ + 764 +++ + 765 +++ ++ 766 +++ ++ 767+++ ++ 768 +++ + 769 +++ + 770 +++ + 771 +++ + 772 +++ + 773 +++ + 774+++ + 775 +++ + 776 +++ ++ 777 +++ + 778 +++ + 779 +++ + 780 +++ + 781+++ + 782 +++ + 783 +++ + 784 +++ + 785 +++ + 786 +++ + 787 +++ + 788+++ ++ 789 +++ + 790 +++ + 791 +++ + 792 +++ + 793 +++ + 794 +++ + 795+++ + 796 +++ ++ 797 +++ + 798 +++ + 799 +++ ++ 800 +++ ++ 801 +++ + 802+++ + 803 +++ + 804 +++ + 805 +++ + 806 +++ + 807 +++ + 808 +++ ++ 809+++ ++ 810 +++ + 811 +++ + 812 +++ + 813 +++ + 814 +++ + 815 +++ ++ 816+++ ++ 817 +++ ++ 818 +++ ++ 819 +++ ++ 820 +++ + 821 +++ + 822 +++ +823 +++ + 824 +++ + 825 +++ 826 +++ ++ 827 +++ + 828 +++ + 829 +++ + 830+++ ++ 831 +++ + 832 +++ + 833 +++ + 834 +++ + 835 +++ + 836 +++ ++ 837+++ + 838 +++ ++ 839 +++ ++ 840 +++ + 841 +++ + 842 +++ + 843 +++ + 844+++ + 845 +++ + 846 +++ + 847 +++ ++ 848 +++ + 849 +++ + 850 +++ ++ 851+++ + 852 +++ + 853 +++ ++ 854 ++ ++ 855 ++ + 856 ++ + 857 ++ ++ 858++ + 859 ++ ++ 860 ++ + 861 ++ ++ 862 ++ + 863 ++ + 864 ++ + 865 ++ ++866 ++ ++ 867 ++ + 868 ++ + 869 ++ + 870 ++ + 871 ++ + 872 ++ + 873 ++++ 874 ++ ++ 875 ++ ++ 876 ++ + 877 ++ + 878 ++ + 879 ++ + 880 ++ + 881++ ++ 882 ++ + 883 ++ ++ 884 ++ ++ 885 ++ + 886 ++ ++ 887 ++ + 888 ++ +889 ++ ++ 890 ++ ++ 891 ++ + 892 ++ + 893 ++ + 894 ++ + 895 ++ + 896++ + 897 ++ + 898 ++ + 899 ++ ++ 900 ++ + 901 ++ + 902 ++ + 903 ++ + 904++ + 905 ++ + 906 ++ + 907 ++ + 908 ++ + 909 ++ + 910 ++ + 911 ++ + 912++ + 913 ++ + 914 ++ + 915 ++ + 916 ++ + 917 ++ + 918 ++ + 919 ++ + 920++ + 921 ++ + 922 ++ + 923 ++ + 924 ++ + 925 ++ + 926 ++ + 927 ++ + 928++ + 929 ++ + 930 ++ + 931 ++ + 932 + + 933 + + 934 + + 935 + + 936 + +937 + + 938 + + 939 + + 940 + + 941 + + 942 + + 943 + + 944 + + 945 +946 + + 947 + + 948 + + 949 + + 950 + + 951 + + 952 + + 953 + + 954 +955 + + 956 + + 957 + + 958 + + 959 + + 960 + + 961 + + 962 + +++

1. A compound of formula (I-h):

or a pharmaceutically acceptable salt thereof, wherein: R¹ is—C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl, —C₃-C₈cycloalkyl,—C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl, —OR⁵, —N(R⁵)₂, or—NHR⁵; R⁴ and R^(4′) are each independently —H, halogen, —OH, —CN, or—NH₂; each R⁵ is independently —C₁-C₆alkyl, —C₃-C₈cycloalkyl,heterocyclyl, aryl, or heteroaryl; R⁶ and R⁷ are each independently, ateach occurrence, —C₁-C₆alkyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, —OH,halogen, oxo, —CN, —SR⁸, —OR⁸, —(CH₂)_(n)—OR⁸, —NHR⁸, —NR⁸R⁹,—S(O)₂NR⁸R⁹, —S(O)₂R^(8′), —C(O)R^(8′), —C(O)OR⁸, —C(O)NR⁸R⁹,—NR⁸C(O)R^(9′), —NR'S(O)₂R^(9′), —S(O)R^(8′), —S(O)NR⁸R⁹, or—NR⁸S(O)R^(9′), wherein each alkyl, cycloalkyl, heterocyclyl,spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰; R⁸ and R⁹ are each independently, ateach occurrence, —H, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl, heteroaryl,wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,heterocyclyl, aryl, or heteroaryl is optionally substituted with one ormore R¹⁰ or R¹¹; or R⁸ and R⁹ may combine with the atom to which theyare both attached to form a —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl,wherein the formed —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl,spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl isoptionally substituted with one or more R¹⁰ or R¹¹; R^(8′) and R^(9′)are each independently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, aryl,heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionallysubstituted with one or more R¹⁰ or R¹¹; or R^(8′) and R^(9′) maycombine with the atom to which they are both attached to form a—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, spirocycloalkyl,spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionallysubstituted with one or more R¹⁰ or R¹¹; R¹⁰ and R¹¹ are eachindependently, at each occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl,—C₂-C₆alkynyl, —C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl,heteroaryl, aryl, —OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl,—OC₃-C₆cycloalkyl, -Oaryl, -Oheteroaryl, —NHC₁-C₆alkyl, —N(C₁-C₆alkyl)₂,—S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂, —S(O)₂C₁-C₆alkyl,—C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl), —C(O)N(C₁-C₆alkyl)₂,—C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl, —S(O)(C₁-C₆alkyl),—S(O)N(C₁-C₆alkyl)₂, or —N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl), wherein eachalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl,heteroaryl, or aryl is optionally substituted with one or more —R²;wherein any two R¹⁰ or any two R¹¹, when on non-adjacent atoms, cancombine to form a bridging cycloalkyl or heterocyclyl; wherein any twoR¹⁰ or any two R¹¹, when on adjacent atoms, can combine to form acycloalkyl, heterocyclyl, aryl or heteroaryl; R¹² is independently, ateach occurrence, —C₁-C₆alkyl, —C₂-C₆alkenyl, —C₂-C₆alkynyl,—C₃-C₈cycloalkyl, —C₄-C₈cycloalkenyl, heterocyclyl, heteroaryl, aryl,—OH, halogen, oxo, —NO₂, —CN, —NH₂, —OC₁-C₆alkyl, —NHC₁-C₆alkyl,—N(C₁-C₆alkyl)₂, —S(O)₂NH(C₁-C₆alkyl), —S(O)₂N(C₁-C₆alkyl)₂,—S(O)₂C₁-C₆alkyl, —C(O)C₁-C₆alkyl, —C(O)NH₂, —C(O)NH(C₁-C₆alkyl),—C(O)N(C₁-C₆alkyl)₂, —C(O)OC₁-C₆alkyl, —N(C₁-C₆alkyl)SO₂C₁-C₆alkyl,—S(O)(C₁-C₆alkyl), —S(O)N(C₁-C₆alkyl)₂, or—N(C₁-C₆alkyl)S(O)(C₁-C₆alkyl); and n is an integer from 1 to
 4. 2. Thecompound of claim 1, wherein the compound is a compound of formula(I-h′):


3. The compound of claim 1, wherein the compound is a compound offormula (I-h″):


4. The compound of claim 1, wherein R¹—OR⁵.
 5. The compound of claim 4,wherein R⁵ is —C₁-C₆alkyl.
 6. The compound of claim 4, wherein R⁵ ismethyl.
 7. The compound of claim 1, wherein R⁴ is —H.
 8. The compound ofclaim 1, wherein R^(4′) is —H.
 9. The compound of claim 1, wherein R⁶ isaryl and the aryl is optionally substituted with one or more R¹⁰. 10.The compound of claim 1, wherein R⁶ is phenyl and the phenyl isoptionally substituted with one or more R¹⁰.
 11. The compound of claim9, wherein each R¹⁰ is independently selected from —C₁-C₆alkyl, halogen,and —OC₁-C₆alkyl.
 12. The compound of claim 1, wherein R⁷ is selectedfrom —OH, —CN, —OR, —(CH₂)_(n)—OR⁸, and —S(O)₂R^(8′).
 13. The compoundof claim 12, wherein R⁷ is —OR⁸, and R⁸ is —C₁-C₆alkyl.
 14. The compoundof claim 12, wherein R⁷ is —(CH₂)_(n)—OR⁸, n is 1, and R⁸ is —H.
 15. Thecompound of claim 12, wherein R⁷ is —S(O)₂R^(8′) and R^(8′) is—C₁-C₆alkyl.
 16. A compound selected from the group consisting of:Compound No. Structure Name 143

3-((S)-6-(methoxycarbonyl)-7-methyl-3-((trans)-4-(methylsulfonyl)cyclohexyl)-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin- 2-yl)-2-phenylpropanoicacid 144

3-((S)-6-(methoxycarbonyl)-7-methyl-3-((trans)-4-(methylsulfonyl)cyclohexyl)-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin- 2-yl)-2-phenylpropanoicacid 151

3-((S)-6-(methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 152

3-((S)-6-(methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 153

3-((S)-3-((trans)-4-cyanocyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 154

3-((S)-3-((trans)-4-cyanocyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 159

3-((S)-3-((cis)-3- (hydroxymethyl)cyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 160

3-((S)-3-((cis)-3- (hydroxymethyl)cyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 161

3-((S)-3-((cis)-3- (hydroxymethyl)cyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 162

3-((S)-3-((cis)-3- (hydroxymethyl)cyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 163

3-((S)-3-((trans)-3- (hydroxymethyl)cyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 164

3-((S)-3-((trans)-3- (hydroxymethyl)cyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 165

3-((S)-3-((trans)-3- (hydroxymethyl)cyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 166

3-((S)-3-((trans)-3- (hydroxymethyl)cyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 167

2-(3-fluorophenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 168

2-(3-fluorophenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 169

2-(4-fluorophenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 170

2-(4-fluorophenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 171

2-(3-chlorophenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 172

2-(3-chlorophenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 173

2-(4-chlorophenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 174

2-(4-chlorophenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 175

2-(3,4-difluorophenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 176

2-(3,4-difluorophenyl)-3- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 177

3-((S)-6-(methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- (m-tolyl)propanoic acid178

3-((S)-6-(methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- (m-tolyl)propanoic acid179

3-((S)-6-(methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- (p-tolyl)propanoic acid180

3-((S)-6-(methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- (p-tolyl)propanoic acid181

2-(3-fluoro-4-methoxyphenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 182

2-(3-fluoro-4-methoxyphenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 183

2-(3-fluoro-4-methylphenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 184

2-(3-fluoro-4-methylphenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 185

2-(3-chloro-4-methylphenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 186

2-(3-chloro-4-methylphenyl)-3-((S)-6- (methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2- yl)propanoic acid 199

3-((S)-3-((trans)-4-hydroxycyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 200

3-((S)-3-((trans)-4-hydroxycyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 201

3-((S)-3-((1R,3R)-3-hydroxycyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 202

3-((S)-3-((1R,3R)-3-hydroxycyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 203

3-((S)-3-((1R,3S)-3-hydroxycyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 204

3-((S)-3-((1R,3S)-3-hydroxycyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 205

3-((S)-3-((1S,3R)-3-hydroxycyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 206

3-((S)-3-((1S,3R)-3-hydroxycyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 207

3-((S)-3-cyclohexyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoic acid 208

3-((S)-3-cyclohexyl-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoic acid 209

3-((S)-3-((cis)-3-cyanocyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 210

3-((S)-3-((cis)-3-cyanocyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 211

3-((S)-3-((cis)-3-cyanocyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 212

3-((S)-3-((cis)-3-cyanocyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 213

3-((S)-3-((trans)-3-cyanocyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 214

3-((S)-3-((trans)-3-cyanocyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 215

3-((S)-3-((trans)-3-cyanocyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 216

3-((S)-3-((trans)-3-cyanocyclohexyl)-6-(methoxycarbonyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 404

3-((7S)-6-(methoxycarbonyl)-3-(3- methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 455

3-((7S)-6-(methoxycarbonyl)-3-(3- methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 475

3-((7S)-6-(methoxycarbonyl)-3-(3- methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 632

3-((7S)-6-(methoxycarbonyl)-3-(3- methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 757

3-((7S)-6-(methoxycarbonyl)-3-(3- methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid 791

3-((7S)-6-(methoxycarbonyl)-3-(3- methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2- phenylpropanoic acid


17. The compound of claim 1, wherein the compound is the first or secondeluting isomer of

3-((S)-6-(methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)-2-phenylpropanoicacid.
 18. The compound of claim 1, wherein the compound is the first orsecond eluting isomer of

2-(3-chlorophenyl)-3-((S)-6-(methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)propanoicacid.
 19. The compound of claim 1, wherein the compound is the first orsecond eluting isomer of

2-(3-chloro-4-methylphenyl)-3-((S)-6-(methoxycarbonyl)-3-((trans)-4-methoxycyclohexyl)-7-methyl-6,7,8,9-tetrahydro-3H-imidazo[4,5-f]quinolin-2-yl)propanoicacid.
 20. A pharmaceutical composition comprising a compound of claim 1,or a pharmaceutically acceptable salt thereof, and a pharmaceuticallyacceptable carrier.